颞下颌关节滑膜细胞对应力的分子应答机制及丹皮中具有滑膜细胞保护作用的化合物筛选
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摘要
第一部分应力作用对大鼠滑膜细胞形态学的影响
颞下颌关节(temporomandibular joint,TMJ)是人体内保持较强终身改建能力的负重关节。颞下颌关节紊乱病(temporomandibular disorders,TMD)是口腔外科临床的常见病,关节盘前移位(anterior disc displacement,ADD)是其中最常见的类型。因为局部力学环境的改变,关节盘移位后,作为关节运动的两个主要承力区的髁突和关节盘可以发生一系列的适应性改建以适应新的盘突关系。并且滑膜的过量炎症反应被认为是TMD的起始因素之一。然而,临床研究发现一些有症状的关节盘移位患者在不恢复关节盘正常解剖位置的情况下进行保守治疗亦可达良好的疗效。生物力对影响骨关节形态、功能以及软骨生成的重要因素之一。但目前生物力学研究多集中在大骨关节上,对于TMJ盘移位后髁突以及双板区的力学研究较少。
实验一无菌条件下取Sprague-Dawley大鼠双侧TMJ髁突关节盘后区平滑光亮的滑膜组织,用组织块法处理滑膜组织,将培养瓶倒置37℃,5%CO_2培养箱内培养2-3 hrs,使其贴壁。然后翻转继续培养。待有滑膜细胞爬出组织块后,去除组织块,继续培养。3d后可见有梭形细胞贴壁生长。为鉴定分离得到的原代滑膜细胞,分别用巨噬细胞标记物CD68和纤维原细胞标记物vimentin对培养的细胞进行免疫染色。同时设计加载应力模式为静水压力(hydrostatic pressure,HP)0kPa,30kPa,60kPa和90kPa 12 hrs。
结果显示:培养的滑膜细胞贴壁生长,分布均匀,形态均一,呈短梭状,有两个或多个突起,细胞核呈卵圆性,位于细胞中央,核仁明显。培养的原代细胞达铺满状态所需的时间,与分离细胞的存活率和细胞接种密度等有关系,存活率越高,接种密度越大,到达铺满状态所需的时间越短。所有培养的滑膜细胞均对vimentin蛋白表达阳性,CD68蛋白表达阴性,说明该细胞来源于中胚层,并具有成纤维细胞的特点,是滑膜细胞B型细胞,即滑膜成纤维细胞(synovial fibroblasts,SFs)。
实验二分别用MTT法、流式细胞术、超微电镜、免疫染色等方法来检测不同程度的HP对SFs增殖、细胞周期、超微结构以及细胞骨架的影响。
结果显示:MTT结果显示受到不同HP的各组SFs增殖率间不存在显著差异。运用流式细胞术分析细胞周期所得的结果也表明应力组和正常组细胞G2期与G1期细胞数目大致相同。而在不同强度的HP下SFs的F-actin呈现较为不同的变化。正常情况下,F-actin在细胞间呈现大量有序排列的突起,在应力情况下,细胞外形被拉伸,呈现较强的应力纤维染色特征。
不同HP下SFs的超微结构也呈现不同程度的改变。30kPa应力下细胞胞浆和胞核轻度皱缩,在致密的胞浆中可以辨认线粒体等细胞器,核仁明显,较0kPa时变化不大;60kPa作用后发现胞体进一步皱缩,胞膜及其内侧空泡形成,胞核更加致密,但仍可见完整的核膜结构及边聚的染色质,呈新月形或驼峰状;90kPa时SFs的超微结构主要表现为核膜结构不完整,细胞器变性,核内结构少量溶解;胞浆内空泡形成,染色质凝集成块,与核膜分离,残留网状或颗粒状的染色。
当TMJ髁突受到机械负重,关节腔内的应力就会改变。HP就作为一个机械因素,来维持关节腔的稳定性,并且高的HP能够影响细胞结构和细胞分化,干扰细胞膜的流动性和细胞膜的结构以及一些内部的细胞器。SFs作为近些年来对关节组织的研究靶点,能够对机械的、离子的和渗透性的信号有较好的敏感性和传导性;并根据周围环境、激素和基因等因素对所收到的信号做出相应的反馈,进而调节代谢活动。
第二部分应力对滑膜细胞TGF-β、BMP-2和SOX-9表达的影响
迄今为止,应力作用下TMJ软骨重建的机制还未能完全阐明。众多研究表明,双板区滑膜组织内压力的提高主要是由关节盘移位造成,可能引起双板区软骨化生过程和关节的重建。转化生长因子-beta(transforming growth factor beta,TGF-β)和骨形态发生蛋白(bone morphogenetic proteins,BMPs)在骨及软骨的修复,成骨细胞和破骨细胞的分化、增殖过程中都发挥着极其重要的作用:同时TGF-β与BMP-2与其各自的受体结合后能通过细胞内信号系统将信号传递到细胞核内而起到多种不同的生理调节作用。SOX-9基因则是软骨化生的重要指标之一。上一章研究已发现应力作用下,SFs的细胞骨架会发生一定的变化,但应力对SFs生长相关蛋白表达的研究还较少。因此我们通过观察SFs在不同HP作用下TGF-β、BMP-2和SOX-9的表达情况,对应力作用下TMJ的改建机理进行探讨
实验三SFs原代培养和应力加载方式同第一部分实验一。分别用免疫细胞化学和Western Blot法检测不同强度HP作用下的SFs中TGF-β、BMP-2和SOX-9表达情况。对免疫细胞化学结果进行灰度测定,用t检验和单因素方差分析对灰度值进行统计学分析。Western Blot结果用Biosense 300 software软件进行信号分析,以GAPDH蛋白的光密度值进行标准校正,计算TGF-β、BMP-2和SOX-9蛋白产物的相对量。
结果显示:TGF-β和BMP-2在正常细胞表达不高,在HP作用下表达明显增强,但随着HP强度增高,该变化并不明显。SOX-9在30kPa时染色高于正常培养的细胞染色,60kPa时表达增加,90kPa时表达又稍有降低。Western Blot结果与免疫细胞化学的结果一致。
关节负重是维持关节软骨正常组成和功能的基本要求。尽管TMD的发病机理尚不完全清楚,但关节软骨承受的局部生物力对于TMD的发生发展有潜在的促进作用。关节盘移位后,髁突在前移位关节盘的机械刺激下可以发生一系列的改建。关节盘移位后,局部滑膜组织增厚,表明局部有炎性刺激,其受到前移位关节盘的持续存在的牵拉作用,使得双板区应力环境发生改变,滑膜组织的代谢加快达到新的平衡。因而我们有理由认为关节盘移位后TGF-β和BMP-2的表达的升高更多是由于双板区组织受到的机械应力刺激的直接结果。SOX-9的表达在软骨形成早期变化明显,可以成为TMD发生发展过程早期的重要标记。
第三部分应力对滑膜细胞MAPK通路蛋白表达的影响
MAPK信号通路参与多种细胞外刺激引起的细胞反应,在细胞的多项生命活动及对细胞外环境变化引起的适应性改建中发挥重要的调控作用。但对于MAPK通路是否在髁突软骨表达以及在骨组织改建中的作用尚不明确。有实验发现在人滑膜组织的纤维位点发现炎症细胞浸润和TGF-β的过表达,TGF-β的过表达不仅会引起组织纤维化的病理过程,还会影响正常器官的功能。本章对SFs在不同程度HP作用下MAPK通路上三个重要蛋白ERK、JNK和p38的表达及其活化情况进行了检测,初步探讨了上述三个通路在异常应力下的作用。并且加入ERK特异阻断剂PD98059后,观察不同时间点TGF-β的变化。
实验四将原代培养的SFs加载应力后,用Western Blot方法对不同HP作用下MAPK通路上三个重要蛋白ERK、JNK和p38在SFs表达及其活化情况进行检测,初步探讨上述三个通路在异常应力下的作用。
结果显示:与正常细胞相比,30 kPa HP作用显著抑制了ERK蛋白表达,60 kPa时恢复到正常组水平,但90 kPa时又有所降低;而ERK的活化水平在30 kPa时最高,在90 kPa时最低;30 kPa应力作用同时也提高了JNK蛋白的表达,在60 kPa和90 kPa时,JNK的表达依次明显降低;而应力作用对p38的表达以及JNK、p38的磷酸化水平基本无影响。
实验五在原代培养的SFs中加入15μM PD 98059在30kPa HP作用下分别培养5 mins,30 mins,1 hr,2 hrs,4 hrs,8 hrs和12 hrs,以同等应力同等时间点未加入PD 98059收集的细胞作对照。ERK的阻断剂PD98059按照说明书用DMSO溶解,对照组细胞在加载应力前用PD98059孵育1 hr。空白组细胞用0.04%的DMSO孵育。收集细胞培养液并ELISA试剂盒检测在加载应力前加入ERK阻断剂PD98059探讨在ERK/MAPK通路调节应力下TGF-β的作用。
结果显示:SFs在应力作用下TGF-β的分泌量增加,尤其在30kPa作用下分泌量增加较多,而在加入ERK特异抑制剂PD98059后,TGF-β的活性得到了显著抑制。提示在一定的应力作用下SFs可通过提高TGF-β的活性,导致MAPK通路的激活,从而启动自适应性改建过程。
本部分内容侧重分析了SFs在HP作用下三种MAPK亚型,ERK,JNK和p38的表达和活化情况。ERK通路在HP作用下起着重要的调节作用,JNK和p38作用不明显。在30kPaHP作用下加入ERK通路抑制剂PD98059后,SFs分泌TGF-β的活性得到了显著抑制。进一步证明TGF-β介导的ERK通路在SFs受到应力作用下引发的自我适应和调节的过程中起着一定作用。而p38和ERK在成骨过程中起着相反的调节作用,分化活性通过介导黏附分子的表达在前软骨阶段的后期来调节成骨,在本试验中p38的作用较小。
第四部分丹皮中具有滑膜细胞保护作用的化合物筛选
滑膜的过量炎症反应被认为是TMD的起始因素之一。SFs在应力作用下会加大TNF-α等炎症因子的分泌量,以启动后续的病理生理过程。因此可推测,具有抗炎活性的化合物可用于治疗早期的TMD。中药在治疗复杂性疾病、慢性疾病、免疫疾病等方面具有独特的疗效和优势。丹皮提取物能够抑制ROS堆积,并具有自由基清除能力,另一种与丹皮具有类似化学组成的中药材—芍药的提取物,能够在抑制关节炎大鼠的炎症反应,并改变SFs的超微结构。然而,丹皮药材中具有抗炎活性的化合物及其活性,至今少见报道。本部分内容通过活性追踪的方式筛选并鉴定有效成分,确定丹皮提取物及组分的抗炎活性。
实验六运用制备液相色谱分离丹皮提取物得到22个组分,采用实验一介绍的原代培养SFs,加入10 ng/mL的IL-1β刺激后,ELISA法检测培养液中TNF-α含量。并运用液相色谱—质谱联用法对具有活性的组分进行鉴定并分离。
结果显示:分离得到的6个组分能够显著抑制IL-1β刺激后的SFs分泌TNF-α。通过对活性组分的鉴定从中发现8种化学成分。进一步研究分离得到的三种化学成分芍药苷、丹皮酚和五没食子酰葡萄糖对于抑制SFs合成TNF-α和IL-6时均呈现明显的量效关系。
近年来,大量临床和实验研究表明许多中药提取物和中药活性成分是一类安全、有效的骨关节炎和风湿性关节炎治疗药物。研究者通过比较姜黄科的中药材在关节炎小鼠模型上的抗炎活性,找出了一系列有活性的中药提取物。由此可见,有望从中药提取物中找出治疗TMD的药物。以往,TMD常采用保守治疗,也有研究者尝试采用关节内注射超氧化物岐化酶和透明质酸钠的方法进行补充治疗。本部分研究结果表明,丹皮提取物中的一些具有抗炎活性的有效化合物通过控制TMD患者的炎症反应来达到预防和治疗的目的。
结论
1.滑膜细胞在应力作用下形态学和超微结构会发生变化,且这种变化程度与应力大小有关。
2.静水压力能够引起滑膜细胞骨形成相关蛋白的变化,这种改变与力学的大小呈现不同趋势的变化,说明TGF-β、BMP-2和SOX-9对于滑膜细胞在应力作用下起到不同的调节作用。
3.静水压力能引起MAPK通路上ERK、JNK、P38等重要信号分子的改变并引起ERK的活化,提示ERK1/2通路的作用发挥着重要作用。并且TGF-β介导的ERK通路在滑膜细胞应力作用下的自我适应和调节过程中起着信号传导的作用。
4.从丹皮药材中纯化得到的三种活性化合物芍药苷、丹皮酚和五没食子酰葡萄糖能够抑制颞下颌关节滑膜细胞的炎症反应。
Part one:Effects of hydrostatic pressure on cytoskeleton in rat temporomandibular synovial fibroblasts
Temporomandibular disorders(TMD)are common syndromes in dental.clinic and are characterized by orafacial pain,joint sounds,and limited mandibular movement.Several studies have demonstrated that the increased pressure in synovium of the bilaminar zone, chiefly caused by disc displacement,may be contributed to the progression of chondrogenesis in bilaminar zone and remodeling in joint.As a physiological factor,the pressure in joint cavity takes an important role in keeping intra-articular fluid and maintaining the stability of the join.
In part one of this study,the double condyles of 3 months old Sprague-Dawley rats(～200 g)were excised.Surface parts of synovial tissues were isolated from TMJ of rats,followed by washing extensively with phosphate-buffered saline,then minced into 1mm~3 pieces and plated onto tissue culture dishes with DMEM supplemented with 15%fetal calf serum.SFs were confirmed by immunocytochemical staining to detect marker proteins CD68 and vimentin,which are macrophage marker and fibroblasts marker,respectively.SFs were seeded onto the culture dishes at a concentration of 2×10~6 cells/dish.When the cells reached 70%confluence,the culture dishes were transferred to a columned stainless-steel vessel.The vessel was then placed in the cell-culture incubator.HP was applied at levels of 30 kPa,60 kPa,90 kPa for 12 hrs.
Our results showed that the primary cultured cells were found to proliferate with a fibroblastic character,whilst no spontaneous changes in shape were found even in repeated culture.When grown to confluence,the cells looked spindly and polygonal.The cells were confirmed by immunocytochemical staining.All cells were negative for CD68.Moreover, they were all positive for vimentin,a fibroblasts marker and confirmed to be synovial fibroblasts(SFs).
In part two of this study,Changes of proliferation,cell cycle,ultrastructure and cytoskeleton were observed by MTT assay,flow cytometry transmission electron microscope and fluorescent microscope after loading different HP.
Our results showe that the proliferation rates in HP treated groups were lower than 100%, but there were no statistical differences in comparison of cells in normal condition.The result of cell cycle of SFs is the similar.The ultrastructure of SFs at 0kPa was normal and intact.At 30 kPa,the ultrastructure of SFs mostly shows that the chromatin was condensated lightly and ruptured to the nuclear margin.At 60 kPa,the karyon takes on crescent and the mitochondria seem varicose.At 90 kPa,the apoptosis-like body was wrapped by membrane and embedded in the high density chromatin.Compared with the untreated control,the cellular actin configuration of SFs became elongated and more intense F-actin stress fiber staining was observed after HPloading.
The SFs primary cell culture and HP loading were successfully established in this study. Our results suggested that HP could impact on the change of ultrastucture and cytoskeleton of SFs.Meanwhile,SFs could response the HP and might be occurring some molecular eventswhich relative to the new biomechanicai environment.
Part two:Effects of hydrostatic pressure on BMP-2,TGF-βand SOX-9 production in rat temporomandibular synovial fibroblasts
Recent experimental evidence has suggested that pressure may play an important role in the pathogenesis of arthritic diseases such as temporomandibular disorders,rheumatic diseases and osteoarthritis.This study examines the effects of hydrostatic pressure(HP)on the protein production of BMP-2,TGF-βand SOX-9 in SFs of rat TMJ.The primary SFs culture and loading profile were the same as the part one.Production of TGF-β,BMP-2 and SOX-9 was examined by immunocytochemical assay and Western blot.
Exposure of SFs to HP for 12 hrs resulted in significant up-regulation of BMP-2 by 46%,54%,66%at 30,60,90 kPa,whilst TGF-βincreased by 11%,19%and 28%at 30,60, 90kPa.HP also induced the increase of SOX-9 by 72%at 30 kPa and 83%at 60 kPa,but only 54%at 90 kPa.
The obtained data suggests that HP induced the alteration of cytoskeleton and bone-morphogenetic-related proteins production of SFs,which may influence the pathological condition of temporomandibular disorders.
Part three:Effects of hydrostatic pressure on MAPK and TGF-βin rat temporomandibular synovial fibroblasts
Various data obtained mitogen-activated protein kinases(MAPKs)in many types of cells argue that activation of a pathway occurs after loading stimulation.The purpose of the present work is to detect the relationship between ERK,JNK and p38 activation and the magnitude of HP by SFs culture,and examine the change of TGF-βwith or without ERK inhibitor(PD 98059)with time.
The primary SFs culture and loading profile were the same as described before.The first part in this study,protein extracts were analyzed by western blot for the activation of ERK,JNK and p38.
Our results showed that the production and activation of ERK,JNK and p38 were changed with the magnitude of HP.SFs exposured to 30kPa HP showed low expression of ERK,and then returned to normal.Finally,the expression of ERK decreased.On the other way,the activation of ERK shows highest on 30kPa and shows lowest on 90kPa. Meanwhile,30 kPa HP can also change the expression of JNK.But HP has less effect on the activation of JNK and p38.
The second part in this study,SFs were cultured in the HP for a constant time point such as 5 mins,30 mins,1 hr,2 hrs,4 hrs,8 hrs and 12 hrs with or without 15μM PD 98059, an inhibitor of ERK.Cells were pre-incubated with PD 98059 for 1 hr before the mechanical stimulation began.The inhibitor was reconstituted in dimethylsulphoxide (DMSO),and control cells were pre-incubated with equivalent amounts of 0.04%DMSO alone.The TGF-βconcentration was tested by ELISA method.The assay procedure was performed accordi ng to the manufacturer's instructions.
Our results showed that HP especially 30 kPa HP could increase the expression of TGF-β,But the ERK inhibitor PD98059 suppressed HP-induced expression of TGF-β.
These results demonstrate that mechnical pressure induced by HP involved activation of ERK,JNK and p38 with different level.Mechanical stimulation induced a rapid activation of ERK,resulting in a visible phosphorylation at 30 kPa.On contract,the production of JNK and p38 changed along with the different HP,but the change of both phosphorylations is not visible.It indicates that JNK and p38 are not sensitive to the HP. There is a relationship between ERK and TGF-βassociated with HP.which may be play a key rolein remodeling of injured SF.
Part four:screening of Moutan Cortex for anti-inflammatory activities and chemical constituents
Moutan Cortex,a widely used traditional Chinese medicine for the treatment of various diseases,is the root bark of Paeonia suffruticosa Andrews(Paeoniaceae).Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities,antioxidant and sedative actions.Otherwise,there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex.The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex.
With the aid of preparative HPLC technique,ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions.Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-alpha(TNF-α)on rat synovial fibroblasts subjected to interleukin-1beta(IL-1β).Eight compounds were isolated from six active fractions and identified by HPLC/MS~n.Purified compounds,paeoniflorin,paeonol, and pentagalloylglucose resulted in dose-dependent inhibition of TNF-αand IL-6 synthesis in synoviocytes treated with proinflammatory mediator.
Traditionally,temporomandibular disorder(TMD)is treated with conservative therapy. Some alternative and complementary therapy for TMD patients have also been introduced, including intra-articular injection of superoxide dismutase(SOD)and sodium hyaluronate (SH).Evaluation of cell viability indicated that incubation of synoviocytes with fractions of Moutan Cortex for 1 d at concentration of 10~(-5)g/ml dose not reduce the percent of viable cells.These results suggested that paeonol,paeoniflorin,glycosides and pentagalloylglucose has potential to be used as anti-inflammatory drug for patients with TMD.
Condusion:
1.HP could impact on the change of cytoskeleton and ultrastructure of SFs after exposure in HP,and the direct proportion along with HP.
2.TGF-βand BMP-2 might regulate the remodeling of the mandibular condyle induced by the mechanical stimulation during the disc displacement.SOX-9 would be a valuable parameter of cartilage regeneration
3.The production and activation of ERK1/2 could be changed by different magnitude of HP and HP has less effect on activation of JNK and p38.ERK1/2 plays an important role in SFs suffering HP and transfer the signal by TGF-β.
4.Paeonol,paeoniflorin,glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex to SFs.
颞下颌关节(temporomandibular joint,TMJ)是人体内保持较强终身改建能力的负重关节。颞下颌关节紊乱病(temporomandibular disorders,TMD)是口腔外科临床的常见病,关节盘前移位(anterior disc displacement,ADD)是其中最常见的类型。因为局部力学环境的改变,关节盘移位后,作为关节运动的两个主要承力区的髁突和关节盘可以发生一系列的适应性改建以适应新的盘突关系。并且滑膜的过量炎症反应被认为是TMD的起始因素之一。然而,临床研究发现一些有症状的关节盘移位患者在不恢复关节盘正常解剖位置的情况下进行保守治疗亦可达良好的疗效。生物力对影响骨关节形态、功能以及软骨生成的重要因素之一。但目前生物力学研究多集中在大骨关节上,对于TMJ盘移位后髁突以及双板区的力学研究较少。
实验一无菌条件下取Sprague-Dawley大鼠双侧TMJ髁突关节盘后区平滑光亮的滑膜组织,用组织块法处理滑膜组织,将培养瓶倒置37℃,5%CO_2培养箱内培养2-3 hrs,使其贴壁。然后翻转继续培养。待有滑膜细胞爬出组织块后,去除组织块,继续培养。3d后可见有梭形细胞贴壁生长。为鉴定分离得到的原代滑膜细胞,分别用巨噬细胞标记物CD68和纤维原细胞标记物vimentin对培养的细胞进行免疫染色。同时设计加载应力模式为静水压力(hydrostatic pressure,HP)0kPa,30kPa,60kPa和90kPa 12 hrs。
结果显示:培养的滑膜细胞贴壁生长,分布均匀,形态均一,呈短梭状,有两个或多个突起,细胞核呈卵圆性,位于细胞中央,核仁明显。培养的原代细胞达铺满状态所需的时间,与分离细胞的存活率和细胞接种密度等有关系,存活率越高,接种密度越大,到达铺满状态所需的时间越短。所有培养的滑膜细胞均对vimentin蛋白表达阳性,CD68蛋白表达阴性,说明该细胞来源于中胚层,并具有成纤维细胞的特点,是滑膜细胞B型细胞,即滑膜成纤维细胞(synovial fibroblasts,SFs)。
实验二分别用MTT法、流式细胞术、超微电镜、免疫染色等方法来检测不同程度的HP对SFs增殖、细胞周期、超微结构以及细胞骨架的影响。
结果显示:MTT结果显示受到不同HP的各组SFs增殖率间不存在显著差异。运用流式细胞术分析细胞周期所得的结果也表明应力组和正常组细胞G2期与G1期细胞数目大致相同。而在不同强度的HP下SFs的F-actin呈现较为不同的变化。正常情况下,F-actin在细胞间呈现大量有序排列的突起,在应力情况下,细胞外形被拉伸,呈现较强的应力纤维染色特征。
不同HP下SFs的超微结构也呈现不同程度的改变。30kPa应力下细胞胞浆和胞核轻度皱缩,在致密的胞浆中可以辨认线粒体等细胞器,核仁明显,较0kPa时变化不大;60kPa作用后发现胞体进一步皱缩,胞膜及其内侧空泡形成,胞核更加致密,但仍可见完整的核膜结构及边聚的染色质,呈新月形或驼峰状;90kPa时SFs的超微结构主要表现为核膜结构不完整,细胞器变性,核内结构少量溶解;胞浆内空泡形成,染色质凝集成块,与核膜分离,残留网状或颗粒状的染色。
当TMJ髁突受到机械负重,关节腔内的应力就会改变。HP就作为一个机械因素,来维持关节腔的稳定性,并且高的HP能够影响细胞结构和细胞分化,干扰细胞膜的流动性和细胞膜的结构以及一些内部的细胞器。SFs作为近些年来对关节组织的研究靶点,能够对机械的、离子的和渗透性的信号有较好的敏感性和传导性;并根据周围环境、激素和基因等因素对所收到的信号做出相应的反馈,进而调节代谢活动。
第二部分应力对滑膜细胞TGF-β、BMP-2和SOX-9表达的影响
迄今为止,应力作用下TMJ软骨重建的机制还未能完全阐明。众多研究表明,双板区滑膜组织内压力的提高主要是由关节盘移位造成,可能引起双板区软骨化生过程和关节的重建。转化生长因子-beta(transforming growth factor beta,TGF-β)和骨形态发生蛋白(bone morphogenetic proteins,BMPs)在骨及软骨的修复,成骨细胞和破骨细胞的分化、增殖过程中都发挥着极其重要的作用:同时TGF-β与BMP-2与其各自的受体结合后能通过细胞内信号系统将信号传递到细胞核内而起到多种不同的生理调节作用。SOX-9基因则是软骨化生的重要指标之一。上一章研究已发现应力作用下,SFs的细胞骨架会发生一定的变化,但应力对SFs生长相关蛋白表达的研究还较少。因此我们通过观察SFs在不同HP作用下TGF-β、BMP-2和SOX-9的表达情况,对应力作用下TMJ的改建机理进行探讨
实验三SFs原代培养和应力加载方式同第一部分实验一。分别用免疫细胞化学和Western Blot法检测不同强度HP作用下的SFs中TGF-β、BMP-2和SOX-9表达情况。对免疫细胞化学结果进行灰度测定,用t检验和单因素方差分析对灰度值进行统计学分析。Western Blot结果用Biosense 300 software软件进行信号分析,以GAPDH蛋白的光密度值进行标准校正,计算TGF-β、BMP-2和SOX-9蛋白产物的相对量。
结果显示:TGF-β和BMP-2在正常细胞表达不高,在HP作用下表达明显增强,但随着HP强度增高,该变化并不明显。SOX-9在30kPa时染色高于正常培养的细胞染色,60kPa时表达增加,90kPa时表达又稍有降低。Western Blot结果与免疫细胞化学的结果一致。
关节负重是维持关节软骨正常组成和功能的基本要求。尽管TMD的发病机理尚不完全清楚,但关节软骨承受的局部生物力对于TMD的发生发展有潜在的促进作用。关节盘移位后,髁突在前移位关节盘的机械刺激下可以发生一系列的改建。关节盘移位后,局部滑膜组织增厚,表明局部有炎性刺激,其受到前移位关节盘的持续存在的牵拉作用,使得双板区应力环境发生改变,滑膜组织的代谢加快达到新的平衡。因而我们有理由认为关节盘移位后TGF-β和BMP-2的表达的升高更多是由于双板区组织受到的机械应力刺激的直接结果。SOX-9的表达在软骨形成早期变化明显,可以成为TMD发生发展过程早期的重要标记。
第三部分应力对滑膜细胞MAPK通路蛋白表达的影响
MAPK信号通路参与多种细胞外刺激引起的细胞反应,在细胞的多项生命活动及对细胞外环境变化引起的适应性改建中发挥重要的调控作用。但对于MAPK通路是否在髁突软骨表达以及在骨组织改建中的作用尚不明确。有实验发现在人滑膜组织的纤维位点发现炎症细胞浸润和TGF-β的过表达,TGF-β的过表达不仅会引起组织纤维化的病理过程,还会影响正常器官的功能。本章对SFs在不同程度HP作用下MAPK通路上三个重要蛋白ERK、JNK和p38的表达及其活化情况进行了检测,初步探讨了上述三个通路在异常应力下的作用。并且加入ERK特异阻断剂PD98059后,观察不同时间点TGF-β的变化。
实验四将原代培养的SFs加载应力后,用Western Blot方法对不同HP作用下MAPK通路上三个重要蛋白ERK、JNK和p38在SFs表达及其活化情况进行检测,初步探讨上述三个通路在异常应力下的作用。
结果显示:与正常细胞相比,30 kPa HP作用显著抑制了ERK蛋白表达,60 kPa时恢复到正常组水平,但90 kPa时又有所降低;而ERK的活化水平在30 kPa时最高,在90 kPa时最低;30 kPa应力作用同时也提高了JNK蛋白的表达,在60 kPa和90 kPa时,JNK的表达依次明显降低;而应力作用对p38的表达以及JNK、p38的磷酸化水平基本无影响。
实验五在原代培养的SFs中加入15μM PD 98059在30kPa HP作用下分别培养5 mins,30 mins,1 hr,2 hrs,4 hrs,8 hrs和12 hrs,以同等应力同等时间点未加入PD 98059收集的细胞作对照。ERK的阻断剂PD98059按照说明书用DMSO溶解,对照组细胞在加载应力前用PD98059孵育1 hr。空白组细胞用0.04%的DMSO孵育。收集细胞培养液并ELISA试剂盒检测在加载应力前加入ERK阻断剂PD98059探讨在ERK/MAPK通路调节应力下TGF-β的作用。
结果显示:SFs在应力作用下TGF-β的分泌量增加,尤其在30kPa作用下分泌量增加较多,而在加入ERK特异抑制剂PD98059后,TGF-β的活性得到了显著抑制。提示在一定的应力作用下SFs可通过提高TGF-β的活性,导致MAPK通路的激活,从而启动自适应性改建过程。
本部分内容侧重分析了SFs在HP作用下三种MAPK亚型,ERK,JNK和p38的表达和活化情况。ERK通路在HP作用下起着重要的调节作用,JNK和p38作用不明显。在30kPaHP作用下加入ERK通路抑制剂PD98059后,SFs分泌TGF-β的活性得到了显著抑制。进一步证明TGF-β介导的ERK通路在SFs受到应力作用下引发的自我适应和调节的过程中起着一定作用。而p38和ERK在成骨过程中起着相反的调节作用,分化活性通过介导黏附分子的表达在前软骨阶段的后期来调节成骨,在本试验中p38的作用较小。
第四部分丹皮中具有滑膜细胞保护作用的化合物筛选
滑膜的过量炎症反应被认为是TMD的起始因素之一。SFs在应力作用下会加大TNF-α等炎症因子的分泌量,以启动后续的病理生理过程。因此可推测,具有抗炎活性的化合物可用于治疗早期的TMD。中药在治疗复杂性疾病、慢性疾病、免疫疾病等方面具有独特的疗效和优势。丹皮提取物能够抑制ROS堆积,并具有自由基清除能力,另一种与丹皮具有类似化学组成的中药材—芍药的提取物,能够在抑制关节炎大鼠的炎症反应,并改变SFs的超微结构。然而,丹皮药材中具有抗炎活性的化合物及其活性,至今少见报道。本部分内容通过活性追踪的方式筛选并鉴定有效成分,确定丹皮提取物及组分的抗炎活性。
实验六运用制备液相色谱分离丹皮提取物得到22个组分,采用实验一介绍的原代培养SFs,加入10 ng/mL的IL-1β刺激后,ELISA法检测培养液中TNF-α含量。并运用液相色谱—质谱联用法对具有活性的组分进行鉴定并分离。
结果显示:分离得到的6个组分能够显著抑制IL-1β刺激后的SFs分泌TNF-α。通过对活性组分的鉴定从中发现8种化学成分。进一步研究分离得到的三种化学成分芍药苷、丹皮酚和五没食子酰葡萄糖对于抑制SFs合成TNF-α和IL-6时均呈现明显的量效关系。
近年来,大量临床和实验研究表明许多中药提取物和中药活性成分是一类安全、有效的骨关节炎和风湿性关节炎治疗药物。研究者通过比较姜黄科的中药材在关节炎小鼠模型上的抗炎活性,找出了一系列有活性的中药提取物。由此可见,有望从中药提取物中找出治疗TMD的药物。以往,TMD常采用保守治疗,也有研究者尝试采用关节内注射超氧化物岐化酶和透明质酸钠的方法进行补充治疗。本部分研究结果表明,丹皮提取物中的一些具有抗炎活性的有效化合物通过控制TMD患者的炎症反应来达到预防和治疗的目的。
结论
1.滑膜细胞在应力作用下形态学和超微结构会发生变化,且这种变化程度与应力大小有关。
2.静水压力能够引起滑膜细胞骨形成相关蛋白的变化,这种改变与力学的大小呈现不同趋势的变化,说明TGF-β、BMP-2和SOX-9对于滑膜细胞在应力作用下起到不同的调节作用。
3.静水压力能引起MAPK通路上ERK、JNK、P38等重要信号分子的改变并引起ERK的活化,提示ERK1/2通路的作用发挥着重要作用。并且TGF-β介导的ERK通路在滑膜细胞应力作用下的自我适应和调节过程中起着信号传导的作用。
4.从丹皮药材中纯化得到的三种活性化合物芍药苷、丹皮酚和五没食子酰葡萄糖能够抑制颞下颌关节滑膜细胞的炎症反应。
Part one:Effects of hydrostatic pressure on cytoskeleton in rat temporomandibular synovial fibroblasts
Temporomandibular disorders(TMD)are common syndromes in dental.clinic and are characterized by orafacial pain,joint sounds,and limited mandibular movement.Several studies have demonstrated that the increased pressure in synovium of the bilaminar zone, chiefly caused by disc displacement,may be contributed to the progression of chondrogenesis in bilaminar zone and remodeling in joint.As a physiological factor,the pressure in joint cavity takes an important role in keeping intra-articular fluid and maintaining the stability of the join.
In part one of this study,the double condyles of 3 months old Sprague-Dawley rats(～200 g)were excised.Surface parts of synovial tissues were isolated from TMJ of rats,followed by washing extensively with phosphate-buffered saline,then minced into 1mm~3 pieces and plated onto tissue culture dishes with DMEM supplemented with 15%fetal calf serum.SFs were confirmed by immunocytochemical staining to detect marker proteins CD68 and vimentin,which are macrophage marker and fibroblasts marker,respectively.SFs were seeded onto the culture dishes at a concentration of 2×10~6 cells/dish.When the cells reached 70%confluence,the culture dishes were transferred to a columned stainless-steel vessel.The vessel was then placed in the cell-culture incubator.HP was applied at levels of 30 kPa,60 kPa,90 kPa for 12 hrs.
Our results showed that the primary cultured cells were found to proliferate with a fibroblastic character,whilst no spontaneous changes in shape were found even in repeated culture.When grown to confluence,the cells looked spindly and polygonal.The cells were confirmed by immunocytochemical staining.All cells were negative for CD68.Moreover, they were all positive for vimentin,a fibroblasts marker and confirmed to be synovial fibroblasts(SFs).
In part two of this study,Changes of proliferation,cell cycle,ultrastructure and cytoskeleton were observed by MTT assay,flow cytometry transmission electron microscope and fluorescent microscope after loading different HP.
Our results showe that the proliferation rates in HP treated groups were lower than 100%, but there were no statistical differences in comparison of cells in normal condition.The result of cell cycle of SFs is the similar.The ultrastructure of SFs at 0kPa was normal and intact.At 30 kPa,the ultrastructure of SFs mostly shows that the chromatin was condensated lightly and ruptured to the nuclear margin.At 60 kPa,the karyon takes on crescent and the mitochondria seem varicose.At 90 kPa,the apoptosis-like body was wrapped by membrane and embedded in the high density chromatin.Compared with the untreated control,the cellular actin configuration of SFs became elongated and more intense F-actin stress fiber staining was observed after HPloading.
The SFs primary cell culture and HP loading were successfully established in this study. Our results suggested that HP could impact on the change of ultrastucture and cytoskeleton of SFs.Meanwhile,SFs could response the HP and might be occurring some molecular eventswhich relative to the new biomechanicai environment.
Part two:Effects of hydrostatic pressure on BMP-2,TGF-βand SOX-9 production in rat temporomandibular synovial fibroblasts
Recent experimental evidence has suggested that pressure may play an important role in the pathogenesis of arthritic diseases such as temporomandibular disorders,rheumatic diseases and osteoarthritis.This study examines the effects of hydrostatic pressure(HP)on the protein production of BMP-2,TGF-βand SOX-9 in SFs of rat TMJ.The primary SFs culture and loading profile were the same as the part one.Production of TGF-β,BMP-2 and SOX-9 was examined by immunocytochemical assay and Western blot.
Exposure of SFs to HP for 12 hrs resulted in significant up-regulation of BMP-2 by 46%,54%,66%at 30,60,90 kPa,whilst TGF-βincreased by 11%,19%and 28%at 30,60, 90kPa.HP also induced the increase of SOX-9 by 72%at 30 kPa and 83%at 60 kPa,but only 54%at 90 kPa.
The obtained data suggests that HP induced the alteration of cytoskeleton and bone-morphogenetic-related proteins production of SFs,which may influence the pathological condition of temporomandibular disorders.
Part three:Effects of hydrostatic pressure on MAPK and TGF-βin rat temporomandibular synovial fibroblasts
Various data obtained mitogen-activated protein kinases(MAPKs)in many types of cells argue that activation of a pathway occurs after loading stimulation.The purpose of the present work is to detect the relationship between ERK,JNK and p38 activation and the magnitude of HP by SFs culture,and examine the change of TGF-βwith or without ERK inhibitor(PD 98059)with time.
The primary SFs culture and loading profile were the same as described before.The first part in this study,protein extracts were analyzed by western blot for the activation of ERK,JNK and p38.
Our results showed that the production and activation of ERK,JNK and p38 were changed with the magnitude of HP.SFs exposured to 30kPa HP showed low expression of ERK,and then returned to normal.Finally,the expression of ERK decreased.On the other way,the activation of ERK shows highest on 30kPa and shows lowest on 90kPa. Meanwhile,30 kPa HP can also change the expression of JNK.But HP has less effect on the activation of JNK and p38.
The second part in this study,SFs were cultured in the HP for a constant time point such as 5 mins,30 mins,1 hr,2 hrs,4 hrs,8 hrs and 12 hrs with or without 15μM PD 98059, an inhibitor of ERK.Cells were pre-incubated with PD 98059 for 1 hr before the mechanical stimulation began.The inhibitor was reconstituted in dimethylsulphoxide (DMSO),and control cells were pre-incubated with equivalent amounts of 0.04%DMSO alone.The TGF-βconcentration was tested by ELISA method.The assay procedure was performed accordi ng to the manufacturer's instructions.
Our results showed that HP especially 30 kPa HP could increase the expression of TGF-β,But the ERK inhibitor PD98059 suppressed HP-induced expression of TGF-β.
These results demonstrate that mechnical pressure induced by HP involved activation of ERK,JNK and p38 with different level.Mechanical stimulation induced a rapid activation of ERK,resulting in a visible phosphorylation at 30 kPa.On contract,the production of JNK and p38 changed along with the different HP,but the change of both phosphorylations is not visible.It indicates that JNK and p38 are not sensitive to the HP. There is a relationship between ERK and TGF-βassociated with HP.which may be play a key rolein remodeling of injured SF.
Part four:screening of Moutan Cortex for anti-inflammatory activities and chemical constituents
Moutan Cortex,a widely used traditional Chinese medicine for the treatment of various diseases,is the root bark of Paeonia suffruticosa Andrews(Paeoniaceae).Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities,antioxidant and sedative actions.Otherwise,there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex.The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex.
With the aid of preparative HPLC technique,ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions.Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-alpha(TNF-α)on rat synovial fibroblasts subjected to interleukin-1beta(IL-1β).Eight compounds were isolated from six active fractions and identified by HPLC/MS~n.Purified compounds,paeoniflorin,paeonol, and pentagalloylglucose resulted in dose-dependent inhibition of TNF-αand IL-6 synthesis in synoviocytes treated with proinflammatory mediator.
Traditionally,temporomandibular disorder(TMD)is treated with conservative therapy. Some alternative and complementary therapy for TMD patients have also been introduced, including intra-articular injection of superoxide dismutase(SOD)and sodium hyaluronate (SH).Evaluation of cell viability indicated that incubation of synoviocytes with fractions of Moutan Cortex for 1 d at concentration of 10~(-5)g/ml dose not reduce the percent of viable cells.These results suggested that paeonol,paeoniflorin,glycosides and pentagalloylglucose has potential to be used as anti-inflammatory drug for patients with TMD.
Condusion:
1.HP could impact on the change of cytoskeleton and ultrastructure of SFs after exposure in HP,and the direct proportion along with HP.
2.TGF-βand BMP-2 might regulate the remodeling of the mandibular condyle induced by the mechanical stimulation during the disc displacement.SOX-9 would be a valuable parameter of cartilage regeneration
3.The production and activation of ERK1/2 could be changed by different magnitude of HP and HP has less effect on activation of JNK and p38.ERK1/2 plays an important role in SFs suffering HP and transfer the signal by TGF-β.
4.Paeonol,paeoniflorin,glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex to SFs.
引文
1.Tallents RH,Katzberg RW,Murphy W,Proskin H.Magnetic resonance imaging findings in asymptomatic volunteers and symptomatic patients with temporomandibular disorders.J Prosthet Dent 1996;75(5):529-533.
2.Goldstein BH.Temporomandibular disorders:a review of current understanding.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88(4):379-385.
3.Feng JY,Zhang K,Gu ZY,Shibata T.[Gene expression changes of cartilage matrix of condylar cartilage with anterior disc displacement].Hua Xi Kou Qiang Yi Xue Za Zhi 2004;22(2):100-102,119.
4.Williams GM,Lin JW,Sah RL.Cartilage Reshaping via In Vitro Mechanical Loading.Tissue Eng 2007;13(12):2903-2911.
5.Huang J,Ballou LR,Hasty KA.Cyclic equibiaxial tensile strain induces both anabolic and catabolic responses in articular chondrocytes Gene 2007;404(1-2):101-109.
6.Weinberg JB,Fermor B,Guilak F.Nitric oxide synthase and cyclooxygenase interactions in cartilage and meniscus:relationships to joint physiology,arthritis,and tissue repair.Subcell Biochem 2007;42:31-62.
7.Dell'Accio F,De Bari C,El Tewil NM,et al.Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury.Arthritis Res Ther 2006;8(5):R139.
8.Yoshikawa S,Nodai E,Habu M,Furuta N,Fukuda J,Yamaguchi K.Influence of altered occlusal plane on rabbit temporomandibular joint cartilage.J Oral Pathol Med 2008;37(1):30-37.
9.Tanaka E,Kikuchi K,Sasaki A,Tanne K.An adult case of TMJ osteoarthrosis treated with splint therapy and the subsequent orthodontic occlusal reconstruction:adaptive change of the condyle during the treatment.Am J Orthod Dentofacial Orthop 2000;118(5):566-571.
10.Breul R.Biomechanical analysis of stress distribution in the temporomandibular joint.Ann Anat 2007;189(4):329-335.
11.Mandrioli S,Polito J,Denes SA,Clauser L.Synovial chondromatosis of the temporomandibular joint.J Craniofac Surg 2007;18(6):1486-1488.
12.Nagai H,Miyamoto Y,Nakata A,Hatakeyana S,Iwanarni Y,Fukuda M.Isolation and characterization of synovial cells from the human temporomandibular joint.J Oral Pathol Med 2006;35(2):104-110.
13.Ogura N,Tobe M,Sakamaki H,et al.Interleukin-1beta increases RANTES gene expression and production in synovial fibroblasts from human temporomandibular joint.J Oral Pathol Med 2004;33(10):629-633.
14.Milam SB,Schmitz JP.Molecular biology of temporomandibular joint disorders:proposed mechanisms of disease.J Oral Maxillofac Surg 1995;53(12):1448-1454.
15.Stevens CR,Blake DR,Merry P,Revell PA,Levick JR.A comparative study by morphometry of the microvasculature in normal and rheumatoid synovium.Arthritis Rheum 1991;34(12):1508-1513.
16.Gu Z,Feng J,Shibata T,Hu J,Zhang Z.Type Ⅱ collagen and aggrecen mRNA expression by in situ hybridization in rabbit temporomandibular joint posterior attachment following disc displacement.Arch Oral Biol 2003;48(1):55-62.
17.Gu Z,Zhou Y,Zhang Y,Zhao S,Liu J,Hu J.An animal model for inducing anterior disc displacement of the temporomandibular joint.J Orofac Pain 2006;20(2):166-173.
[1]Cooper BC,Kleinberg I.Examination of alarge patient population for the presence of symptoms and signs of temporomandibular disorders.Cranio 2007;25:114-26.
[2]Quinn TM,Allen RG,Schalet BJ,Perumbuli P,Hunziker EB.Matrix and cell injury due to sub-impact loading of adult bovine articular cartilage explants.effects of strain rate and peek stress.J Orthop Res 2001;19:242-9.
[3]Fitzgerald JB,Jin M,Chai DH,Siparsky P,Fanning P,Grodzinsky AJ.Sheer- and compression-induced chondrocyte transcription requires MAPK activation in cartilage explants.J Biol Chem 2007.
[4]Leipzig ND,Athanasiou K.Static compression of single chondrocytes catabolically modifies single cell gene expression.Biophys J 2007.
[5]Sachs BL,Goldberg VM,Getzy LL,Moskowitz RW,Malemud CJ.A histopathologic differentiation of tissue types in human osteoarthritic cartilage.J Rheumatol 1982;9:210-6.
[6]Goronzy JJ,Wayand CM.Rheumatoid arthritis.I mmunol Rev 2005;204:55-73.
[7]Scaife S,Brown R,Kellie S,Filer A,Martin S,Thomas AM,et al.Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display.Rheumatology (Oxford)2004;43:1346-52.
[8]Komuro I,Katoh Y,Kaida T,Shibazaki Y,Kurabayashi M,Hoh E,et al.Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes.Possible roleof protein kinase C activation.J Biol Chem 1991;266:1265-8.
[9]Sadoshima J,Takahashi T,Jahn L,Izumo S Roles of mechano-sensitive ion channels,cytoskeleton,and contractile activity in stretch-induced immediate-early gene expression and hypertrophy of cardiac myocytes.Proc Natl Acad Sci USA 1992;89:9905-9.
[10]Lee JH,Fitzgerald JB,Dimicco MA,Grodzinsky AJ.Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression.Arthritis Rheum 2005;52:2386-95.
[11]Honda K,Ohno S,Tanimoto K,Ijuin C,Tanaka N,Doi T,et al.The effects of high magnitude cyclic tensileload on cartilage matrix metabolism in cultured chondrocytes.Eur J Cell Biol 2000;79:601-9.
[12]Noriega S,Mamedov T,Turner JA,Subramanian A.Intermittent applications of continuous ultrasound on the viability,proliferation,morphology,and matrix production of chondrocytes in 3D matrices.Tissue Eng 2007;13:611-8.
[13]Gavenis K,Kremer A,Von Walter M,Hollander DA,Schneider U,Schmidt-Rohlfing B.Effects of cyclic hydrostatic pressure on the metabolism of human osteoarthritic chondrocytes cultivated in a collagen gel.Artif Organs 2007;31:91-8.
[14]Chen Y J,Zhang M,Wang JJ.Study on the effects of mechanical pressure to the ultrastructure and secretion ability of mandibular condylar chondrocytes.Arch Oral Biol 2007;52:173-81.
[15]Fuchs TF,Petersen W,VordemvenneT,Stange R,Raschke M,Paletta JR.Influence of synovial fluid on human osteoblasts:an in vitro study.ScientificWorldJournal 2007;7:2012-20.
[16]Wu HC,Wang TW,Kang PL,Tsuang YH,Sun JS,Lin FH.Coculture of endothelial and smooth muscle cells on a collagen membrane in the development of a small-diameter vascular graft.Biomaterials 2006.
[17]Ozawa H,Imamura K,Abe E,Takahashi N,Hiraide T,Shibasaki Y,et al.Effect of a continuously applied compressive pressure on mouse osteoblast-like cells(MC3T3-E1)in vitro.J Cell Physiol 1990;142:177-85.
[18]Nagai H,Miyamoto Y,Nakata A,Hatakeyama S,Iwanami Y,Fukuda M.Isolation and characterization of synovial cells from the human temporomandibular joint.J Oral Pathol Med 2006;35:104-10.
[19]Wakamatsu K,Nanki T,Miyasaka N,Umezawa K,Kubota T.Effect of a small molecule inhibitor of nuclear factor-kappaB nuclea- translocation in a murine model of arthritis and cultured human synovial cells.Arthritis Res Ther 2005;7:R1348-59.
[20]Fioravanti A,Moretti E,Scapigliati G,Cervone R,Galeazzi M,Collodel G.Morphological,immunocytochemical and biochemical studies in human osteoarthdtic chondrocytes exposed to IL-1b and cyclical hydrostatic pressure Clin Exp Rheumatol 2007;25:690-5.
[21]Arai S,Kawarai T,Arai R,Yoshida M,Furukawa S,Ogihara H,et al.Cessation of Cytokinesis in Schizosaccharomyces pombe during Growth after Release from High Hydrostatic Pressure Treatment.Biosci Biotechnol Biochem 2008.
[22]Chahine NO,Hung CT,Ateshian GA.In-situ measurements of chondrocyte deformation under transient loading.Eur Cell Mater 2007;13:100-11;discussion 11.
[23]Choi SH,Hwang SB.Modulation of the transforming growth factor-beta signal transduction pathway by hepatitis C virus nonstructural 5A prote n.J Biol Chem 2006;281:7468-78.
[24]Monfort J,Garcia-Giralt N,Lopez-Armeda M J,Monllau JC,Bonilla A,Benito P,et al.Decreased metalloproteinase production as a response to mechanical pressure in human cartilage:a mechanism for homeostatic regulation.Arthritis Res Ther 2006;8:R149.
[25]Wong M,Carter DR.Articular cartilage functional histomorphology and mechanobiology:a research perspective Bone 2003;33:1-13.
[26]Hall AC,Urban JP,Gehl KA.The effects of hydrostatic pressure on matrix synthesis in articular cartilage J Orthop Res 1991;9:1-10.
[27]Parkkinen JJ,Lammi MJ,Pelttari A,Helminen HJ,Tammi M,Virtanen I.Altered Golgi apparatus in hydrostatically Ioaded articular cartilage chondrocytes.Ann Rheum Dis 1993;52:192-8.
[28]Lammi MJ,Inkinen R,Parkkinen JJ,Hakkinen T,Jortikka M,Nelimarkka LO,et al.Expression of reduced amounts of structurally altered aggrecan in articular cartilage chondrocytes exposed to high hydrostatic pressure.Biochem J 1994;304(Pt 3):723-30.
[29]Parkkinen JJ,Lammi M J,Inkinen R,Jortikka M,Tammi M,Virtanen I,et al.Influence of short-term hydrostatic pressure on organization of stress fibers in cultured chondrocytes.J Orthop Res 1995;13:495-502.
[30]Ishihara H,McNally DS,Urban JP,Hall AC.Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk.J Appl Physiol 1996;80:839-46.
[31]Levick JR.The influence of hydrostatic pressure on trans-synovial fluid movement and on capsular expansion in the rabbit knee.J Physiol 1979;289:69-82.
[32]Handa T,Ishihara H,Ohshima H,Osada R,Tsuji H,Obata K.Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.Spine 1997;22:1085-91.
[33]Kaarniranta K,Holmberg CI,Lammi MJ,Eriksson JE,Sistonen L,Heiminen HJ.Primary chondrocytes resist hydrostatic pressure-induced stress while primary synovial cells and fibroblasts show modified Hsp70 response.Osteoarthritis Cartilage 2001;9:7-13.
[34]Schett G,Redlich K,Xu Q,Bizan P,Groger M,Tohidast-Akrad M,et al.Enhanced expression of heat shock protein 70(hsp70)and heat shock factor 1(HSF1)activation in rheumatoid arthritis synovial tissue.Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines,shear stress,and antiinflammatory drugs.J Clin Invest 1998;102:302-11.
[35]Gu Z,Wu H,Feng J,Shibata T,Hu J,Zhang Y,et al.Adaptive alterations of elastic fibers in the bilaminar zone of rabbit temporomandibular joint following disc displacement.Chin Med J(Engl)2002;115:1772-6.
[36]Gu Z,Feng J,Shibata T,Hu J,Zhang Z.Type Ⅱ collagen and aggrecan mRNA expression by in situ hybridization in rabbit temporomandibular joint posterior attachment following disc displacement.Arch Oral Biol 2003;48:55-62.
[37]Ravosa MJ,Kunwar R,Stock SR,Stack MS.Pushing the limit:masticatory stress and adaptive plasticity in mammalian craniomandibular joints.J Exp Biol 2007;210:628-41.
[38]Poli A,Scott D,Bertin K,Miserocchi G,Mason RM,Levick JR.Influence of actin cytoskeleton on intra-articular and interstitial fluid pressure in synovial joints.Microvasc Res 2001;62:293-305.
[39]Mentre P,Hamraoui L,Hui Bon Hoa G,Debey P.Pressure-sensitivity of endoplasmic reticulum membrane and nucleolus as revealed by electron microscopy.Cell Mol Biol(Noisy-le-grand)1999;45:353-62.
[40]Ribeiro CM,Reece J,Putney JW,Jr.Role of the cytoskeleton in calcium signaling in NIH 3T3 cells.An intact cytoskeleton is required for agonist-induced[Ca2+]i signaling,but not for capacitative calcium entry.J Biol Chem 1997;272:26555-61.
[41]Polistena A,Johnson LB,Ohiami-Masseron S,Wittgren L,Back S,Thornberg C,et al.Local radiotherapy of exposed murine small bowel:Apoptosis and inflammation.BMC Surg 2008;8:1.
[42]Liu JJ,He H,Zhang Z,Jiang SX,Akahoshi T,Yang J,et al.Mitochondria Play a Role in the Development of Non-Apoptotic Programmed Cell Death of Neutrophils Induced by ONO-AE-248.Cell Mol Immunol 2007;4:447-53.
[43]de Waard V,Arkenbout EK,Vos M,Mocking AI,Niessen HW,Stooker W,et al.TR3 nuclear orphan receptor prevents cyclic stretch-induced proliferation of venous smooth muscle cells.Am J Pathol 2006;168:2027-35.
[44]Kishikawa H,Miura S,Yoshida H,Hirokawa M,Nakamizo H,Higuchi H,et al.Transmural pressure induces IL-6 secretion by intestinal epithelial cells.Clin Exp Immunol 2002;129:86-91.
[45]Hsieh MH,Nguyen HT.Molecular rnechanism of apoptosis induced by mechanical foroes.Int Rev Cytol 2005;245:45-90.
[46]Islam N,Haqqi TM,Jepsen KJ,Kraay M,Welter JF,Goldberg VM,et al.Hydrostatic pressure induces apoptosis in human chondrocytes from osteoarthritic cartilage through up-regulation of tumor necrosis factor-alpha,inducible nitric oxide synthase,p53,c-myc,and bax-alpha,and suppression of bcl-2.J Cell Biochem 2002;87:266-78.
[47]Attur MG,Dave M,Akamatsu M,Katoh M,Amin AR.Osteoarthritis or osteoarthrosis:the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine.Osteoarthritis Cartilage 2002;10:1-4.
[1]Coleman PJ,Scott D,Abiona A,Ashhurst DE,Mason RM,Levick JR.Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium.J Physiol 1998;509(Pt 3):695-710.
[2]Koshino T,Wada S,Ara Y,Saito T.Regeneration of degenerated articular cartilage after high tibial valgus osteotomy for medial compartmental osteoarthritis of the knee.Knee 2003;10:229-36.
[3]van der Meulen MC,Beaupre GS,Smith RL,Giddings VL,Allen WA,Athanasiou KA,et al.Fsctors influencing changes in articular cartilage following hemiarthroplasty in sheep.J Orthop Res 2002;20:669-75.
[4]Gu Z,Jin X,Feng J,Shibata T,Hu J,Zhan J,et al.Type Ⅱ collagen and aggrecan mRNA expressions in rabbit condyle following disc displacement.J Oral Rehabil 2005;32:254-9.
[5]Almarza AJ,Athanasiou KA.Effects of hydrostatic pressure on TMJ disc cells.Tissue Eng 2006;12:1285-94.
[6]Choi SH,Hwang SB.Modulation of the transforming growth factor-beta signal transduction pathway by hepatitis C virus nonstructural 5A protein.J Biol Chem 2006;281:7468-78.
[7]Huang SA,Mulcahey MA,Crescenzi A,Chung M,Kim BW,Barnes C,et al.Transforming growth factor-beta promotes inactivation of extracellular thyroid hormones via transcriptional stimulation of type 3 iodothyronine deiodinase.Mol Endocrinol 2005;19:3126-36.
[8]Shah AK,Lazatin J,Sinha RK,Lennox T,Hickok NJ,Tuan RS.Mechanism of BMP-2 stimulated adhesion of osteoblastic cells to titanium alloy.Biol Cell 1999;91:131-42.
[9]Kawakami Y,Rodriguez-Leon J,Belmonte JC.The role of TGFbetas and Sox9 during limb chondrogenesis.Curr Opin Cell Biol 2006;18:723-9.
[10]Mizuno S,Tateishi T,Ushida T,Glowacki J.Hydrostatic fluid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture.J Cell Physiol 2002;193:319-27.
[11]DeLise AM,Fischer L,Tuan RS.Cellular interactions and signaling in cartilage development.Osteoarthritis Cartilage 2000;8:309-34.
[12]Darling EM,Athanasiou KA.Growth factor impact on articular cartilage subpopulations.Cell Tissue Res 2005;322:463-73.
[13]Dell'Accio F,De Bari C,El Tawil NM,Barone F,Mitsiadis TA,O'Dowd J,et al.Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury.Arthritis Res Ther 2006;8:R139.
[14]Kaarniranta K,Elo M,Sironen R,Lammi MJ,Goldring MB,Eriksson JE,et al.Hsp70 accumulation in chondrocytic cells exposed to high continuous hydrostatic pressure coincides with mRNA stabilization rather than transcriptional activation.Proc Natl Acad Sci U S A 1998;95:2319-24.
[15]Palmoski MJ,Colyer RA,Brandt KD.Joint motion in the absence of normal loading does not maintain normal articular cartilage.Arthritis Rheum 1980;23:325-34.
[16]Kiviranta I,Jurvelin J,Tammi M,Saamanen AM,Helminen HJ.Weight bearing controls glyoosaminoglycan concentration and articular cartilage thickness in the knee joints of young beagle dogs Arthritis Rheum 1987;30:801-9.
[17]Fujimura K,Kobayashi S,Suzuki T,Segami N.Histologic evaluation of temporomandibular arthritis induced by mild mechanical loading in rabbits J Oral Pathol Med 2005;34:157-63.
[18]Tanimoto K,Suzuki A,Ohno S,Honda K,Tanaka N,Doi T,et al.Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint.J Dent Res 2004;83:40-4.
[19]Perez del Palomar A,Doblare M.An accurate simulation model of anteriorly displaced TMJ discs with and without reduction.Med Eng Phys 2007;29:216-26.
[20]Kirkbride KC,Townsend TA,Bruinsma MW,Barnett JV,Blobe GC.Bone morphogenetic proteins signal through the transforming growth factor-beta type Ⅲ receptor.J Biol Chem 2008.
[21]Katagiri T,Takahashi N.Regulatory mechanisms of osteoblast and osteoclast differentiation.Oral Dis 2002;8:147-59.
[22]Csiszar A,Smith KE,Koller A,Kaley G,Edwards JG,Ungvari Z.Regulation of bone morphogenetic protein-2 expression in endothelial cells role of nuclear factor-kappaB activation by tumor necrosis factor-alpha,H2O2,and high intravascular pressure.Circulation 2005;111:2364-72.
[23]Fantozzi I,Huang W,Zhang J,Zhang S,Platoshyn O,Remillard CV,et al.Divergent effects of BMP-2 on gene expression in pulmonary artery smooth muscle cells from normal subjects and patients with idiopathic pulmonary arterial hypertension.Exp Lung Res 2005;31:783-806.
[24]Wong M,Carter DR.Articular cartilage functional histomorphology and mechanobiology:a research perspective.Bone 2003;33:1-13.
[25]Smith JD,Davies N,Willis AI,Sumpio BE,Zilla P.Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth musde cells.Endothelium 2001;8:41-8.
[26]Schild C,Trueb B.Mechanical stress is required for high-level expression of connective tissue growth factor.Exp Cell Res 2002;274:83-91.
[27]Blain EJ,Gilbert SJ,Wardale RJ,Capper SJ,Mason DJ,Duance VC.Up-regulation of matrix metalloproteinase expression and activation following cyclical compressive loading of articular cartilage in vitro.Arch Biochem Biophys 2001;396:49-55.
[28]Zhang DW,Cole SP,Deeley RG.Determinants of the substrate specificity of multidrug resistance protein 1:role of amino acid residues with hydrogen bonding potential in predicted transmembrane helix 17.J Biol Chem 2002;277:20934-41.
[29]Smith RL,Rusk SF,Ellison BE,Wessells P,Tsuchiya K,Carter DR,et al.In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure.J Orthop Res 1996;14:53-60.
[30]de Crombrugghe B,Lefebvre V,Nakashima K.Regulatory mechanisms in the pathways of cartilage and bone formation.Curr Opin Cell Biol 2001;13:721-7.
[31]Pittenger MF,Mackay AM,Beck SC,Jaiswal RK,Douglas R,Mosca JD,et al.Multilineage potential of adult human mesenchymal stem cells,Science 1999;284:143-7.
[32]Worster AA,Brower-Toland BD,Fortier LA,Bent SJ,Williams J,Nixon AJ.Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1in monolayer and insulin-like growth factor-I in a three-dimensional matrix.J Orthop Res 2001;19:738-49.
[33]Majumdar MK,Wang E,Morris EA.BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.J Cell Physiol 2001;189:275-84.
[34]Sekiya I,Colter DC,Prockop DJ.BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells.Biochem Biophys Res Commun 2001;284:411-8.
[35]Gelse K,von der Mark K,Aigner T,Park J,Schneider H.Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells.Arthritis Rheum 2003;48:430-41.
[36]Jiang J,Nicoll SB,Lu HH.Co-culture of osteoblasts and chondrocytes modulates cellular differentiation in vitro.Biochem Biophys Res Commun 2005;338:762-70.
[37]Fernandes PM.How does yeast respond to pressure? Braz J Med Biol Res 2005;38:1239-45.
[38]Shim JW,Elder SH.Influence of cyclic hydrostatic pressure on fibrocatilaginous metaplasia of achilles tendon fibroblasts.Biomech Model Mechanobiol 2006;5:247-52.
[39]Miyanishi K,Trindade MC,Lindsey DP,Beaupre GS,Carter DR,Goodman SB,et al.Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells in vitro.Tissue Eng 2006;12:2253-62.
[40]Henson FM,Vincent T.Chondrocyte outgrowth into a gelatin scaffold in a single impact load model of damage/repeir-effect of BMP-2.BMC Musculoskelet Disord 2007;8:120.
[41]Miyamoto C,Matsumoto T,Sakimura K,Shindo H.Osteogenic protein-1 with transforming growth factor-beta1:potent induce of chondrogenesis of synovial mesenchymal stem cells in vitro.J Orthop Sci 2007;12:555-61.
[42]Hanada K,Solchaga LA,Caplan AI,Hering TM,Goldberg VM,Yoo JU,et al.BMP-2 induction and TGF-beta 1 modulation of rat periosteal cell chondrogenesis.J Cell Biochem 2001;81:284-94.
[43]Soltz MA,Basalo IM,Ateshian GA.Hydrostatic pressurization and depletion of trapped lubricant pool during creep contact of a rippled indenter against a biphasic articular cartilage layer.J Biomech Eng 2003;125:585-93.
[44]Bell DM,Leung KK,Wheatley SC,Ng LJ,Zhou S,Ling KW,st al.SOX9 directly regulates the type-Ⅱ collagen gene.Nat Genet 1997;16:174-8.
[45]Finger AR,Sargent CY,Dulaney KO,Bernacki SH,Loboa EG.Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure.Tissue Eng 2007;13:1151-8.
[46]Wong M,Siegrist M,Goodwin K.Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primay chondrocytes.Bone 2003;33:685-93.
[47]Adams MA.The mechanical environment of chondrocytes in articular cartilage.Biorheology 2006;43:537-45.
[48]Voulgari PV,Papazisi D,Bai M,Zagorianakou P,Assimakopoulos D,Drosos AA.Laryngeal involvement in rheumatoid arthritis.Rheumatol Int 2005;25:321-5.
[49]Buckwalter JA.Articular cartilage injuries.Clin Orthop Relat Res 2002:21-37.
[50]Tanaka H,Murphy CL,Murphy C,Kimura M,Kawai S,Polak JM.Chondrogenic differentiation of murine embryonic stem cells.effects of culture oonditions and dexamethasone.J Cell Biochem 2004;93:454-62.
[1]Finlay GA,Thannickal VJ,Fanburg BL,Paulson KE.Transforming growth factor-beta 1-induced activation of the ERK pathway/activator protein-1 in human lung fibroblasts requires the autocrine induction of basic fibroblast growth factor.J Biol Chem 2000;275:27650-6.
[2]Stanton LA,Underhill TM,Beier F.MAP kinases in chondrocyte differentiation.Dev Biol 2003;263:165-75.
[3]Seger R,Krebs EG.The MAPK signaling cascade.FASEB J 1995;9:726-35.
[4]Hagemann C,Blank JL.The ups and downs of MEK kinase interactions.Cell Signal 2001;13:863-75.
[5]Kyriakis JM,Avruch J.Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation.Physiol Rev 2001;81:807-69.
[6]Kapur S,Baylink DJ,Lau KH.Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways.Bone 2003;32:241-51.
[7]Han Z,Boyle DL,Aupperle KR,Bennett B,Manning AM,Firestein GS.Jun N-terminal kinase in rheumatoid arthritis.J Pharmacol Exp Ther 1999;291:124-30.
[8]Murakami S,Munsta T,Ezura Y,Furuya K,Yamamoto H.Quantitative analysis of synovial fibrosis in the infrapatellar fat pad before and after anterior cruciate ligament reconstruction.Am J Sports Med 1997;25:29-34.
[9]Shull MM,Ormsby I,Kier AB,Pawlowski S,Diebold RJ,Yin M,et al.Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.Nature 1992;359:693-9.
[10]Massague J,Blain SW,Lo RS.TGFbsta signaling in growth control,cancer,and heritable disorders.Cell 2000;103:295-309.
[11]Moses HL,Yang EY,Pietenpol JA.TGF-bsta stimulation and inhibition of cell proliferation:new mechanistic insights Cell 1990;63:245-7.
[12]Border WA,Noble NA.Transforming growth factor beta in tissue fibrosis.N Engl J Med 1994;331:1286-92.
[13]Qin YX,McLeod KJ,Guilak F,Chiang FP,Rubin CT.Correlation of bony ingrowth to the distribution of stress and strain parameters surrounding a porous-coated implant.J Orthop Res 1996;14:862-70.
[14]Badorff C,Ruetten H,Mueller S,Stahmer M,Gehring D,Jung F,et al.Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces cardiac hypertrophy following pressure overload.J Clin Invest 2002;109:373-81.
[15]Su B,Karin M.Mitogen-activated protein kinase cascades and regulation of gene expression.Curr Opin Immunol 1996;8:402-11.
[16]Nishida E,Gotoh Y.The MAP kinase cascade is essential for diverse signal transduction pathways.Trends Biochem Sci 1993;18:128-31.
[17]Bardwell L.Mechanismsof MAPK signalling specificity.Biochem Soc Trans 2006;34:837-41.
[18]Sundaram MV.RTK/Ras/MAPK signaling.WormBook 2006:1-19.
[19]Hoffman LM,Weston AD,Underhill TM.Molecular mechanisms regulating chondroblast differentiation.J Bone Joint Surg Am 2003;85-A Suppl 2:124-32.
[20]Kumar A,Middleton A,Chambers TC,Mehta KD.Differential roles of extracellular signal-regulated kinase-1/2 and p38(MAPK)in interleukin-1beta- and tumor necrosis factor-alpha-inducad low density lipoprotein receptor expression in HepG2 cells.J Biol Chem 1998;273:15742-8.
[21]Singh RP,Dhawan P,Golden C,Kapoor GS,Mehta KD.One-way cross-talk between p38(MAPK)and p42/44(MAPK).Inhibition of p38(MAPK)induces low density lipoprotein receptor expression through activation of the p42/44(MAPK)cascade.J Biol Chem 1999;274:19593-600.
[22]Lai CF,Chaudhary L,Fausto A,Halstead LR,Ory DS,Avioli LV,et al.Erk is essential for growth,differentiation,integrin expression,and cell function in human osteoblastic cells J Biol Chem 2001;276:14443-50.
[23]Takeuchi Y,Suzawa M,Kikuchi T,Nishida E,Fujita T,Matsumoto T.Differentiation and transforming growth factor-beta receptor down-regulation by collagen-alpha2beta1 integrin interaction is mediated by focal adhesion kinase and its downstream signals in murine osteoblastic cells.J Biol Chem 1997;272:29309-16.
[24]Fraser D,Brunskill N,Ito T,Phillips A.Long-term exposure of proximal tubular epithelial cells to glucose induces transforming growth factor-beta 1 synthesis via an autocrine PDGF loop.Am J Pathol 2003;163:2565-74.
[25]Yoshimura H,Nakahama K,Safronova O,Tanaka N,Muneta T,Morita I.Transforming growth factor-beta stimulates IL-1beta-induced monocyte chemoattractant protein-1 expression in human synovial cells via the ERK/AP-1 pathway.Inflamm Res 2006;55:543-9.
[26]Klein-Nulend J,Roelofsen J,Semeins CM,Bronckers AL,Burger EH.Mechanical stimulation of osteopontin mRNA expression and synthesis in bone cell cultures.J Cell Physiol 1997;170:174-81.
[27]Roelofsen J,Klein-Nulend J,Burger EH.Mechanical stimulation by intermittent hydrolytic compression promotes bone-specific gene expression in vitro.J Biomech 1995;28:1493-503.
[28]Jaiswal RK,Jaiswal N,Bruder SP,Mbalaviele G,Marshak DR,Pittenger MF.Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulaed by mitogen-activated protein kinase.J Biol Chem 2000;275:9645-52.
[29]Cortizo AM,Lettieri MG,Barrio DA,Mercer N,Etcheverry SB,McCarthy AD.Advanced glycation end-products(AGEs)induce concerted changes in the osteoblastic expression of their receptor RAGE and in the activation of extracellular signal-regulated kinases(ERK).Mol Cell Biochem 2003;250:1-10.
[30]Oh CD,Chang SH,Yoon YM,Lee SJ,Lee YS,Kang SS,et al.Opposing role of mitogen-activated protein kinase subtypes,erk-1/2 and p38,in the regulation of chondrogenesis of mesenchymes.J Biol Chem 2000;275:5613-9.
[31]Adams JL,Badge AM,Kumar S,Lee JC.p38 MAP kinase:molecular target for the inhibition of pro-inflammatory cytokines.Prog Med Chem 2001;38:1-60.
[32]Schett G,Tohidast-Akrad M,Smolen JS,Schmid BJ,Steiner CW,Bitzan P,et al.Activation,differential localization,and regulation of the stress-activated protein kinases,extracellular signal-regulated kinase,c-JUN N-terminal kinase,and p38 mitogen-activated protein kinase,in synovial tissue and cells in rheumatoid arthritis.Arthritis Rheum 2000;43:2501-12.
[33]Lee DJ,Rosenfeldt H,Grinnell F.Activation of ERK and p38 MAP kinases in human fibroblasts during collagen matrix contraction.Exp Cell Res 2000;257:190-7.
[34]Wahl SM.Transforming growth factor beta the good,the bad,and the ugly.J Exp Med 1994;180:1567-90.
[35]Robinson FL,Whitehurst AW,Raman M,Cobb MH.Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1.J Biol Chem 2002;277:14844-52.
[36]Takeshita A,Chen Y,Watanabe A,Kiteno S,Hanazawa S.TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells.J Immunol 1995;155:419-26.
[37]Nanki T,Nagasaka K,Hayashida K,Saita Y,Miyasaka N.Chemokines regulate IL-6 and IL-8production by fibroblast-like synoviocytes from patients with rheumatoid arthritis.J Immunol 2001;167:5381-5.
[38]Chen W,Jin W,Cook M,Weiner HL,Wahl SM.Oral delivery of group A streptococcal cell walls augments circulating TGF-beta and suppresses streptococcal cell wall arthritis.J Immunol 1998;161:6297-304.
[39]Song XY,Gu M,Jin WW,Klinman DM,Wahl SM.Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.J Clin Invest 1998;101:2615-21.
[40]Massague J,Wotton D.Transcriptional control by the TGF-beta/Smad signaling system.EMBO J 2000;19:1745-54.
[41]Yamaguchi K,Shirakabe K,Shibuya H,Irie K,Oishi I,Ueno N,et al.Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction.Science 1995;270:2008-11.
[42]Yu L,Hebert MC,Zhang YE.TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses.EMBO J 2002;21:3749-59.
[43]Zavadil J,Bitzer M,Liang D,Yang YC,Massimi A,Kneitz S,et al.Genetic programs of epithelial dell plasticity directed by transforming growth factor-beta.Proc Natl Acad Sci U S A 2001;98:6686-91.
[44]Alessi DR,Cuenda A,Cohen P,Dudley DT,Saltiel AR.PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo.J Biol Chem 1995;270:27489-94.
[45]Lee SW,Choi KY,Cho JY,Jung SH,Song KB,Park EK,et al.TGF-beta2 stimulates cranial suture closure through activation of the Erk-MAPK pathway.J Cell Biochem 2006;98:981-91.
[1]Sambajon VV,Cillo JE,Jr.,Gassner RJ,Buckley MJ.The effects of mechanical strain on synovial fibroblasts.J Oral Maxillofac Surg 2003;61:707-12.
[2]Chiquet M,Renedo AS,Huber F,Fluck M.How do fibroblasts translate mechanical signals into changes in extracellular matrix production? Matrix Biol 2003;22:73-80.
[3]Gynther GW,Dijkgraaf LC,Reinholt FP,Holmlund AB,Liem RS,de Bont LG.Synovial inflammation in arthroscopically obtained biopsy specimens from the temporomandibular joint:a review of the literature and a proposed histologic grading system.J Oral Maxillofac Surg 1998;56:1281-6;discussion 7.
[4]Dijkgraaf LC,Liem RS,van der Weele LT,de Bont LG.Correlation between arthroscopically observed changes and synovial light microscopic findings in osteoarthritic temporomandibular joints.Int J Oral Maxillofac Surg 1999;28:83-9.
[5]Gynther GW,Holmlund AB,Reinholt FP.Synovitis in internal derangement of the temporomandibular joint:correlation between arthroscopic and histologic findings.J Oral Maxillofac Surg 1994;52:913-7;discussion 8.
[6]姜潇.牡丹皮药理作用的研究进展.中国新医药 2004;3:110-1.
[7]Li Y,Zhang W,Huang L,Shi J.[Pharmacological of cortex moutan and core].Zhongguo Zhong Yao Za Zhi 1997;22:214-6,54.
[8]吴少华,马云保.罗晓东.丹皮的化学成分研究.中草药 2002;33:679-80.
[9]Matsuda H,Ohta T,Kawaguchi A,Yoshikawa M.Bioactive constituents of chinese natural medicines.Ⅵ.Mouten cortex.(2):structures and radical scavenging effects of suffruticosides A,B,C,D,and E and galloyl-oxypaeoniflorin.Chem Pharm Bull(Tokyo)2001;49:69-72.
[10]Rho S,Chung HS,Kang M,Lee E,Cho C,Kim H,et al.Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of moutan cortex radicis in oxidative stressed PC12 cells.Biol Pharm Bull 2005;28:661-6.
[11]Zheng YQ,We W.Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes.Int Immunopharmacol 2005;5:1560-73.
[12]Kamimura D,Ishihara K,Hirano T.IL-6 signal transduction and its physiological roles:the signal orchestration model.Rev Physiol Biochem Pharmacol 2003;149:1-38.
[13]Okuda Y,Bardin CW,Hodgskin LR,Morris PL.Interleukins-1 alpha and -1 beta regulate interleukin-6 expression in Leydig and Sertoli cells.Recent Prog Horm Res 1995;50:367-72.
[14]Ogura N,Tobe M,Sakamaki H,Kujiraoka H,Akiba M,Abiko Y,et al.Interleukin-1 beta induces interleukin-6 mRNA expression and protein production in synovial cells from human temporomandibular joint.J Oral Pathol Med 2002;31:353-60.
[15]Kawai Y,Kubota E,Okabe E.Reactive oxygen species participation in experimentally induced arthritis of the temporomandibular joint in rats.J Dent Res 2000;79:1489-95.
[16]Kubota E,Kubota T,Matsumoto J,Shibata T,Murakami KI.Synovial fluid cytokines and proteinases as markers of temporomandibular joint disease.J Oral Maxillofac Surg 1998;56:192-8.
[17]Kubota E,Imamura H,Kubota T,Shibata T,Murakami K.Interleukin 1 beta and stromelysin (MMP3)activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint.J Oral Maxillofac Surg 1997;55:20-7;discussion 7-8.
[18]Sandler NA,Buckley MJ,Cillo JE,Braun TW.Correlation of inflammatory cytokines with arthroscopic findings in patients with temporomandibular joint internal derangements.J Oral Maxillofac Surg 1998;56:534-43;discussion 43-4.
[19]Brown RD,Jones GM,Laird RE,Hudson P,Long CS.Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts.Biochem Biophys Res Commun 2007;362:200-5.
[20]Ahmed S,Anuntiyo J,Malemud CJ,Haqqi TM.Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis:a review.Evid Based Complement Alternat Med 2005;2:301-8.
[21]Genfa L,Jiang Z,Hong Z,Yimin Z,Liangxi W,Guo W,et al.The screening and isolation of an effective anti-endotoxin monomer from Radix Paeoniae Rubra using affinity biosensor technology.Int Immunopharmacol 2005;5:1007-17.
[22]Frondoza CG,Sohrabi A,Polotsky A,Phan PV,Hungerford DS,Lindmark L.An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures.In Vitro Cell Dev Biol Anim 2004;40:95-101.
[23]Kim SH,Kim SA,Park MK,Kim SH,Park YD,Na HJ,et al.Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-alpha.Int Immunopharmacol 2004;4:279-87.
[24]Chou TC.Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia Br J Pharmacol 2003;139:1146-52.
[25]Chun S-C,Jee SY,Lee SG,Park SJ,Lee JR,Kim SC.Anti-Inflammatory Activity of the Methanol Extract of Moutan Cortex in LPS-Activated Raw264.7 Cells.eCAM 2006:nel093.
[26]Tohda C,Nakayama N,Hatanaka F,Komatsu K.Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes:A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.Evid Based Complement Alternat Med 2006;3:255-60.
[27]Lin Y,Pape HD,Friedrich R.Use of superoxide dismutase(SOD)in patients with temporomandibular joint dysfunction--a preliminary study.Int J Oral Maxillofac Surg 1994;23:428-9.
[28]Alpaslan GH,Alpaslan C.Efficacy of temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate in treatment of internal derangemants.J Oral Maxillofac Surg 2001;59:613-8;discussion 8-9.
[29]Zhang G,Yu Z,Zhao H.[Protective effect of paeonol on repeated cerebral ischemia in rats].Zhong Yao Cai 1997;20:626-8.
[30]Lee SE,Hwang HJ,Ha JS,Jeong HS,Kim JH.Screening of medicinal plant extracts for antioxidant activity.Life Sci 2003;73:167-79.
[1]A.Heath C,R.Magari S.Mini-review:Mechanical factors affecting cartilage regeneration in vitro.Biotechnology and Bioengineering 1996;50:430-7.
[2]You L,Temiyasathit S,Lee P,Kim CH,Tummala P,Yao W,et al.Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading.Bone 2008;42:172-9.
[3]Setton LA,Chen J.Mechanobiology of the intervertebral disc and relevance to disc degeneration.J Bone Joint Surg Am 2006;88 Suppl 2:52-7.
[4]Muller S,Labrador V,Dalsla N,Dumas D,Sun R,Wang X,et al.From hemorheology to vascular mechanobiology:An overview.Clin Hemorheol Microcirc 2004;30:185-200.
[5]Kappagoda CT,Ravi K.The rapidly adapting receptors in mammalian airways and their responses to changes in extravascular fluid volume Exp Physiol 2006;91:647-54.
[6]Angele P,Yoo JU,Smith C,Mansour J,Jepsen KJ,Nerlich M,et al.Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro.J Orthop Res 2003;21:451-7.
[7]Martin JS,Brown LS,Haberstroh KM.Microfilaments are involved in renal cell responses to sustained hydrostatic pressure.J Urol 2005;173:1410-7.
[8]Walboomers XF,Elder SE,Bumgardner JD,Jansen JA.Hydrodynamic compression of young and adult rat osteoblast-like cells on titanium fiber mesh.J Biomed Mater Res A 2006;76:16-24.
[9]Barzegar-Jalali M,A dibkia K,Mohammadi G,Zeraati M,Bolagh BA,Nokhodchi A.Propranolol hydrochloride osmotic capsule with controlled onset of release.Drug Deliv 2007;14:461-8.
[10]Ingber DE.Cellular mechanotransduction:putting all the pieces together again.FASEB J 2006;20:811-27.
[11]Sato S,Goto S,Nasu F,Motegi K.Natural course of disc displacement with reduction of the temporomandibular joint:changes in clinical signs and symptoms.J Oral Maxillofac Surg 2003;61:32-4.
[12]Shung KK,Krisko BA,Ballard JO,3rd.Acoustic measurement of erythrocyte compressibility.J Acoust Soc Am 1982;72:1364-7.
[13]Myers KA,Rattner JB,Shrive NG,Hart DA.Hydrostatic pressure sensation in cells:integration into the tensegrity model.Biochem Cell Biol 2007;85:543-51.
[14]Charras GT,Horton MA.Single cell mechanotransduction and its modulation analyzed by atomic force microscope indentation.Biophys J 2002;82:2970-81.
[15]Moosavi-Nejad SF,Hosseni SH,Satoh M,Takayama K.Shock wave induced cytoskeletal and morphological deformations in a human renal carcinoma cell line.Cancer Sci 2006;97:296-304.
[16]Csizmadia V,Raczynski A,Csizmadia E,Fedyk ER,Rottman J,Alden CL.Effect of an experimental proteasome inhibitor on the cytoskeleton,cytosolic protein turnover,and induction in the neuronal cells in vitro.Neurotoxicology 2007.
[17]Schewkunow V,Sharma KP,Diez G,Klemm AH,Sharma PC,Goldmann WH.Thermodynamic evidence of non-muscle myosin Ⅱ-lipid-membrane interaction.Biochem Biophys Res Commun 2008;366:500-5.
[18]Jortikka MO,Parkkinen JJ,Inkinen RI,Karner J,Jarvelainen HT,Nelimarkka LO,et al.The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure.Arch Biochem Biophys 2000;374:172-80.
[19]Frey B,Franz S,Sheriff A,Korn A,Bluemelhuber G,Gaipl US,et al.Hydrostatic pressure induced death of mammalian cells engages pathways related to apoptosis or necrosis.Cell Mol Biol (Noisy-le-grand)2004;50:459-67.
[20]Lammi MJ,Elo MA,Sironen RK,Karjalainen HM,Kaarniranta K,Helminen HJ.Hydrostatic pressure-induced changes in cellular protein synthesis.Biorheology 2004;41:309-13.
[21]Hirsch C,Gauss R,Sommer T.Coping with stress:cellular relaxation techniques.Trends Cell Biol 2006;16:657-63.
[22]Ferreira ST,De Felice FG,Chapeaurouge A.Metastable,partially folded states in the productive folding and in the misfolding and amyloid aggregation of proteins.Cell Biochem Biophys 2006;44:539-48.
[23]Fioravanti A,Moretti E,Scapigliati G Cervone R,Galeazzi M,Collodel G.Morphological,immunocytochemical and biochemical studies in human osteoarthritic chondrocytes exposed to IL-1b and cyclical hydrostatic pressure Clin Exp Rheumatol 2007;25:690-5.
[24]Ishihara H,McNally DS,Urban JP,Hall AC.Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk.J Appl Physiol 1996;80:839-46.
[25]Tesevski V,Sorbetti JM,Chiu SS,Shrive NG,Hart DA.Influence of mechanical and biological signals on gene expression in human MG-63 cells:evidence for a conplex interplay between hydrostatic compression and vitamin D3 or TGF-beta1 on MMP-1 and MMP-3 mRNA levels.Biochem Cell Biol 2005;83:96-107.
[26]Evans CE,Mylchreest S,Andrew JG.Age of donor alters the effect of cyclic hydrostatic pressure on production by human macrophages and osteoblasts of sRANKL,OPG and RANK.BMC Musculoskelet Disord 2006;7:21.
[27]Roelofsen J,Klein-Nulend J,Burger EH.Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro.J Biomech 1995;28:1493-503.
[28]Del Pozo-Insfran D,Del Follo-Martinez A,Talcott ST,Brenes CH.Stability of copigmented anthocyanins and ascorbic acid in muscadine grape juice processed by high hydrestatic pressure.J Food Sci 2007;72:S247-53.
[29]Muir R Sample SJ,Barrett JG,McCarthy J,Vanderby R,Jr.,Markel MD,et al.Effect of fatigue loading and associated matrix microdamage on bone blood flow and interstitial fluid flow.Bone 2007;40:948-56.
[30]Freed LE,Vunjsk-Novakovic G,Marquis JC,Langer R.Kinetics of chondrocyte growth in cell-polymer implants.Biotechnol Bioeng 1994;43:597-604.
[31]Jin G,Sah RL,Li YS,Lotz M,Shyy JY,Chien S.Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes.J Orthop Res 2000;18:899-908.
[32]Lee MS,Trindade MC,Ikenoue T,Schurman DJ,Goodman SB,Smith RL.Effects of shear stress on nitric oxide and matrix protein gene expression in human osteoarthritic chondrocytes in vitro.J Orthop Res 2002;20:556-61.
[33]Palmoski M,Perricone E,Brandt KD.Development and reversal of a proteoglycan aggregation defect in normal canine knee cartilage after immobilization.Arthritis Rheum 1979;22:508-17.
[34]van Kampen GP,Veldhuijzen JP,Kuijer R,van de Stadt RJ,Schipper CA.Cartilage response to mechanical force in high-density chondrocyte cultures.Arthritis Rheum 1985;28:419-24.
[35]Veldhuijzen JP,Huisman AH,Vermeiden JP,Prahl-Andersen B.The growth of cartilage cells in vitro and the effect of intermittent compressive force.A histological evaluation.Connect Tissue Res 1987;16:187-96.
[35]Parkkinen JJ,Ikonen J,Lammi MJ,Laakkonen J,Tammi M,Helminen HJ.Effects of cyclic hydrostatic pressure on proteoglycan synthesis in cultured chondrocytes and articular cartilage explants.Arch Biochem Biophys 1993;300:458-65.
[37]Magari SM.In vitro growth of articular cartilage on a polymer subjected to low levels of intermittent compressive force,Hanover,NH,USA.:Dartmouth College,,1994.
[38]Mizuno S.A novel method for assessing effects of hydrostatic fluid pressure on intracellular calcium:a study with bovine articular chondrocytes.Am J Physiol Cell Physiol 2005;288:C329-37.
[39]Neufeld AH,Liu B.Comparison of the signal transduction pathways for the induction of gene expression of nitric oxide synthase-2 in response to two different stimuli.Nitric Oxide 2003;8:95-102.
[40]Wu HC,Wang TW,Kang PL,Tsuang YH,Sun JS,Lin FH.Coculture of endothelial and smooth muscle cells on a collagen membrane in the development of a small-diameter vascular graft.Biomaterials 2006.
[41]Duwel P,Jungling E,Westhofen M,Luckhoff A.Potassium currents in vestibular type Ⅱ hair cells activated by hydrostatic pressure.Neuroscience 2003;116:963-72.
[42]Salvador-Silva M,Aoi S,Parker A,Yang P,Pecen P,Hernandez MR.Responses and signaling pathways in human optic nerve head astrocytes exposed to hydrostatic pressure in vitro.Glia 2004;45:364-77.
[43]van Oort B,van Hoek A,Ruban AV,van Amerongen H.Equilibrium between quenched and nonquenched conformations of the major plant light-harvesting complex studied with high-pressure time-resolved fluorescence.J Phys Chem B 2007;111:7631-7.
[44]Staves MP.Cytoplasmic streeming and gravity sensing in Chara internodal cells.Planta 1997;203:S79-84.
[45]Cooper ST,Maxwell AL,Kizana E,Ghoddusi M,Hardeman EC,Alexander IE,eL al.C2C12co-culture on a fibroblast substratum enables sustained survival of contractile,highly differentiated myotubes with peripheral nuclei and adult fast myosin expression.Cell Motil Cytoskeleton 2004;58:200-11.
[46]Martinac B.Mechanosensitive ion channels:molecules of mechanotransduction.J Cell Sci 2004;117:2449-60.
[47]Norvell SM,Alvarez M,Bidwell JR,Pavalko FM.Fluid shear stress induces beta-catenin signaling in osteoblasts.Calcif Tissue Int 2004;75:396-404.
[48]Knight MM,Toyoda T,Lee DA,Bader DL.Mechanical compression and hydrostatic pressure induce recersible changes in actin cytoskeletal organisation in chondrocytes in agarose.J Biomech 2006;39:1547-51.
[49]Ayesh EE,Jensen TS,Svensson P.Hypersensitivity to mechanical and intra-articular electrical stimuli in persons with painful temporomandibular joints.J Dent Res 2007;86:1187-92.
[50]Kurz B,Jin M,Patwari P,Cheng DM,Lark MW,Grodzinsky AJ.Biosynthetic response and mechanical properties of articular cartilage after injurious compression.J Orthop Res 2001;19:1140-6.
[51]May B,Saha S,Saltzman M.A three-dimensional mathematical model of temporomandibular joint loading.Clin Biomech(Bristol,Avon)2001;16:489-95.
[52]Tanaka E,Kawai N,Tanaka M,Todoh M,van Eijden T,Hanaoka K,et al.The frictional coefficient of the temporomandibular joint and its dependency on the magnitude and duration of joint loading.J Dent Res 2004;83:404-7.
[53]Sharawy M,All AM,Choi WS.Experimental induction of anterior disk displacement of the rabbit craniomandibular joint:an immuno-electron microscopic study of collagen and proteoglycan occurrence in the condylar cartilage.J Oral Pathol Med 2003;32:176-84.
[54]Franchi M,Trire A,Quaranta M,Orsini E,Ottani V.Collagen structure of tendon relates to function.ScientificWorldJournal 2007;7:404-20.
[55]Schroeder Y,Sivan S,Wilson W,Merkher Y,Huyghe JM,Maroudas A,et al.Are disc pressure,stress,and osmolarity affected by intra- and extrafibrillar fluid exchange? J Orthop Res 2007;25:1317-24.
[56]Tanaka E,Yamano E,Dalla-Bona DA,Watanabe M,Inubushi T,Shirakura M,et al.Dynamic compressive properties of the mandibular condylar cartilage.J Dent Res 2006;85:571-5.
[57]Tanaka E,van Eijden T.Biomechanical behavior of the temporomandibular joint disc.Crit Rev Oral Biol Med 2003;14:138-50.
[58]Hu K,Radhakrishnan P,Patel RV,Mao JJ.Regional structural and viscoelastic properties of fibrocartilage upon dynamic nanoindentation of the articular condyle.J Struct Biol 2001;136:46-52.
[59]Satir P,Chdstensen ST.Overview of structure and function of mammalian cilia.Annu Rev Physiol 2007;69:377-400.
[60]Smith RL,Carter DR,Schurman DJ.Pressure and shear differentially alter human articular chondrocyte metabolism:a review.Clin Orthop Relat Res 2004:S89-95.
2.Goldstein BH.Temporomandibular disorders:a review of current understanding.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88(4):379-385.
3.Feng JY,Zhang K,Gu ZY,Shibata T.[Gene expression changes of cartilage matrix of condylar cartilage with anterior disc displacement].Hua Xi Kou Qiang Yi Xue Za Zhi 2004;22(2):100-102,119.
4.Williams GM,Lin JW,Sah RL.Cartilage Reshaping via In Vitro Mechanical Loading.Tissue Eng 2007;13(12):2903-2911.
5.Huang J,Ballou LR,Hasty KA.Cyclic equibiaxial tensile strain induces both anabolic and catabolic responses in articular chondrocytes Gene 2007;404(1-2):101-109.
6.Weinberg JB,Fermor B,Guilak F.Nitric oxide synthase and cyclooxygenase interactions in cartilage and meniscus:relationships to joint physiology,arthritis,and tissue repair.Subcell Biochem 2007;42:31-62.
7.Dell'Accio F,De Bari C,El Tewil NM,et al.Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury.Arthritis Res Ther 2006;8(5):R139.
8.Yoshikawa S,Nodai E,Habu M,Furuta N,Fukuda J,Yamaguchi K.Influence of altered occlusal plane on rabbit temporomandibular joint cartilage.J Oral Pathol Med 2008;37(1):30-37.
9.Tanaka E,Kikuchi K,Sasaki A,Tanne K.An adult case of TMJ osteoarthrosis treated with splint therapy and the subsequent orthodontic occlusal reconstruction:adaptive change of the condyle during the treatment.Am J Orthod Dentofacial Orthop 2000;118(5):566-571.
10.Breul R.Biomechanical analysis of stress distribution in the temporomandibular joint.Ann Anat 2007;189(4):329-335.
11.Mandrioli S,Polito J,Denes SA,Clauser L.Synovial chondromatosis of the temporomandibular joint.J Craniofac Surg 2007;18(6):1486-1488.
12.Nagai H,Miyamoto Y,Nakata A,Hatakeyana S,Iwanarni Y,Fukuda M.Isolation and characterization of synovial cells from the human temporomandibular joint.J Oral Pathol Med 2006;35(2):104-110.
13.Ogura N,Tobe M,Sakamaki H,et al.Interleukin-1beta increases RANTES gene expression and production in synovial fibroblasts from human temporomandibular joint.J Oral Pathol Med 2004;33(10):629-633.
14.Milam SB,Schmitz JP.Molecular biology of temporomandibular joint disorders:proposed mechanisms of disease.J Oral Maxillofac Surg 1995;53(12):1448-1454.
15.Stevens CR,Blake DR,Merry P,Revell PA,Levick JR.A comparative study by morphometry of the microvasculature in normal and rheumatoid synovium.Arthritis Rheum 1991;34(12):1508-1513.
16.Gu Z,Feng J,Shibata T,Hu J,Zhang Z.Type Ⅱ collagen and aggrecen mRNA expression by in situ hybridization in rabbit temporomandibular joint posterior attachment following disc displacement.Arch Oral Biol 2003;48(1):55-62.
17.Gu Z,Zhou Y,Zhang Y,Zhao S,Liu J,Hu J.An animal model for inducing anterior disc displacement of the temporomandibular joint.J Orofac Pain 2006;20(2):166-173.
[1]Cooper BC,Kleinberg I.Examination of alarge patient population for the presence of symptoms and signs of temporomandibular disorders.Cranio 2007;25:114-26.
[2]Quinn TM,Allen RG,Schalet BJ,Perumbuli P,Hunziker EB.Matrix and cell injury due to sub-impact loading of adult bovine articular cartilage explants.effects of strain rate and peek stress.J Orthop Res 2001;19:242-9.
[3]Fitzgerald JB,Jin M,Chai DH,Siparsky P,Fanning P,Grodzinsky AJ.Sheer- and compression-induced chondrocyte transcription requires MAPK activation in cartilage explants.J Biol Chem 2007.
[4]Leipzig ND,Athanasiou K.Static compression of single chondrocytes catabolically modifies single cell gene expression.Biophys J 2007.
[5]Sachs BL,Goldberg VM,Getzy LL,Moskowitz RW,Malemud CJ.A histopathologic differentiation of tissue types in human osteoarthritic cartilage.J Rheumatol 1982;9:210-6.
[6]Goronzy JJ,Wayand CM.Rheumatoid arthritis.I mmunol Rev 2005;204:55-73.
[7]Scaife S,Brown R,Kellie S,Filer A,Martin S,Thomas AM,et al.Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display.Rheumatology (Oxford)2004;43:1346-52.
[8]Komuro I,Katoh Y,Kaida T,Shibazaki Y,Kurabayashi M,Hoh E,et al.Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes.Possible roleof protein kinase C activation.J Biol Chem 1991;266:1265-8.
[9]Sadoshima J,Takahashi T,Jahn L,Izumo S Roles of mechano-sensitive ion channels,cytoskeleton,and contractile activity in stretch-induced immediate-early gene expression and hypertrophy of cardiac myocytes.Proc Natl Acad Sci USA 1992;89:9905-9.
[10]Lee JH,Fitzgerald JB,Dimicco MA,Grodzinsky AJ.Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression.Arthritis Rheum 2005;52:2386-95.
[11]Honda K,Ohno S,Tanimoto K,Ijuin C,Tanaka N,Doi T,et al.The effects of high magnitude cyclic tensileload on cartilage matrix metabolism in cultured chondrocytes.Eur J Cell Biol 2000;79:601-9.
[12]Noriega S,Mamedov T,Turner JA,Subramanian A.Intermittent applications of continuous ultrasound on the viability,proliferation,morphology,and matrix production of chondrocytes in 3D matrices.Tissue Eng 2007;13:611-8.
[13]Gavenis K,Kremer A,Von Walter M,Hollander DA,Schneider U,Schmidt-Rohlfing B.Effects of cyclic hydrostatic pressure on the metabolism of human osteoarthritic chondrocytes cultivated in a collagen gel.Artif Organs 2007;31:91-8.
[14]Chen Y J,Zhang M,Wang JJ.Study on the effects of mechanical pressure to the ultrastructure and secretion ability of mandibular condylar chondrocytes.Arch Oral Biol 2007;52:173-81.
[15]Fuchs TF,Petersen W,VordemvenneT,Stange R,Raschke M,Paletta JR.Influence of synovial fluid on human osteoblasts:an in vitro study.ScientificWorldJournal 2007;7:2012-20.
[16]Wu HC,Wang TW,Kang PL,Tsuang YH,Sun JS,Lin FH.Coculture of endothelial and smooth muscle cells on a collagen membrane in the development of a small-diameter vascular graft.Biomaterials 2006.
[17]Ozawa H,Imamura K,Abe E,Takahashi N,Hiraide T,Shibasaki Y,et al.Effect of a continuously applied compressive pressure on mouse osteoblast-like cells(MC3T3-E1)in vitro.J Cell Physiol 1990;142:177-85.
[18]Nagai H,Miyamoto Y,Nakata A,Hatakeyama S,Iwanami Y,Fukuda M.Isolation and characterization of synovial cells from the human temporomandibular joint.J Oral Pathol Med 2006;35:104-10.
[19]Wakamatsu K,Nanki T,Miyasaka N,Umezawa K,Kubota T.Effect of a small molecule inhibitor of nuclear factor-kappaB nuclea- translocation in a murine model of arthritis and cultured human synovial cells.Arthritis Res Ther 2005;7:R1348-59.
[20]Fioravanti A,Moretti E,Scapigliati G,Cervone R,Galeazzi M,Collodel G.Morphological,immunocytochemical and biochemical studies in human osteoarthdtic chondrocytes exposed to IL-1b and cyclical hydrostatic pressure Clin Exp Rheumatol 2007;25:690-5.
[21]Arai S,Kawarai T,Arai R,Yoshida M,Furukawa S,Ogihara H,et al.Cessation of Cytokinesis in Schizosaccharomyces pombe during Growth after Release from High Hydrostatic Pressure Treatment.Biosci Biotechnol Biochem 2008.
[22]Chahine NO,Hung CT,Ateshian GA.In-situ measurements of chondrocyte deformation under transient loading.Eur Cell Mater 2007;13:100-11;discussion 11.
[23]Choi SH,Hwang SB.Modulation of the transforming growth factor-beta signal transduction pathway by hepatitis C virus nonstructural 5A prote n.J Biol Chem 2006;281:7468-78.
[24]Monfort J,Garcia-Giralt N,Lopez-Armeda M J,Monllau JC,Bonilla A,Benito P,et al.Decreased metalloproteinase production as a response to mechanical pressure in human cartilage:a mechanism for homeostatic regulation.Arthritis Res Ther 2006;8:R149.
[25]Wong M,Carter DR.Articular cartilage functional histomorphology and mechanobiology:a research perspective Bone 2003;33:1-13.
[26]Hall AC,Urban JP,Gehl KA.The effects of hydrostatic pressure on matrix synthesis in articular cartilage J Orthop Res 1991;9:1-10.
[27]Parkkinen JJ,Lammi MJ,Pelttari A,Helminen HJ,Tammi M,Virtanen I.Altered Golgi apparatus in hydrostatically Ioaded articular cartilage chondrocytes.Ann Rheum Dis 1993;52:192-8.
[28]Lammi MJ,Inkinen R,Parkkinen JJ,Hakkinen T,Jortikka M,Nelimarkka LO,et al.Expression of reduced amounts of structurally altered aggrecan in articular cartilage chondrocytes exposed to high hydrostatic pressure.Biochem J 1994;304(Pt 3):723-30.
[29]Parkkinen JJ,Lammi M J,Inkinen R,Jortikka M,Tammi M,Virtanen I,et al.Influence of short-term hydrostatic pressure on organization of stress fibers in cultured chondrocytes.J Orthop Res 1995;13:495-502.
[30]Ishihara H,McNally DS,Urban JP,Hall AC.Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk.J Appl Physiol 1996;80:839-46.
[31]Levick JR.The influence of hydrostatic pressure on trans-synovial fluid movement and on capsular expansion in the rabbit knee.J Physiol 1979;289:69-82.
[32]Handa T,Ishihara H,Ohshima H,Osada R,Tsuji H,Obata K.Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.Spine 1997;22:1085-91.
[33]Kaarniranta K,Holmberg CI,Lammi MJ,Eriksson JE,Sistonen L,Heiminen HJ.Primary chondrocytes resist hydrostatic pressure-induced stress while primary synovial cells and fibroblasts show modified Hsp70 response.Osteoarthritis Cartilage 2001;9:7-13.
[34]Schett G,Redlich K,Xu Q,Bizan P,Groger M,Tohidast-Akrad M,et al.Enhanced expression of heat shock protein 70(hsp70)and heat shock factor 1(HSF1)activation in rheumatoid arthritis synovial tissue.Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines,shear stress,and antiinflammatory drugs.J Clin Invest 1998;102:302-11.
[35]Gu Z,Wu H,Feng J,Shibata T,Hu J,Zhang Y,et al.Adaptive alterations of elastic fibers in the bilaminar zone of rabbit temporomandibular joint following disc displacement.Chin Med J(Engl)2002;115:1772-6.
[36]Gu Z,Feng J,Shibata T,Hu J,Zhang Z.Type Ⅱ collagen and aggrecan mRNA expression by in situ hybridization in rabbit temporomandibular joint posterior attachment following disc displacement.Arch Oral Biol 2003;48:55-62.
[37]Ravosa MJ,Kunwar R,Stock SR,Stack MS.Pushing the limit:masticatory stress and adaptive plasticity in mammalian craniomandibular joints.J Exp Biol 2007;210:628-41.
[38]Poli A,Scott D,Bertin K,Miserocchi G,Mason RM,Levick JR.Influence of actin cytoskeleton on intra-articular and interstitial fluid pressure in synovial joints.Microvasc Res 2001;62:293-305.
[39]Mentre P,Hamraoui L,Hui Bon Hoa G,Debey P.Pressure-sensitivity of endoplasmic reticulum membrane and nucleolus as revealed by electron microscopy.Cell Mol Biol(Noisy-le-grand)1999;45:353-62.
[40]Ribeiro CM,Reece J,Putney JW,Jr.Role of the cytoskeleton in calcium signaling in NIH 3T3 cells.An intact cytoskeleton is required for agonist-induced[Ca2+]i signaling,but not for capacitative calcium entry.J Biol Chem 1997;272:26555-61.
[41]Polistena A,Johnson LB,Ohiami-Masseron S,Wittgren L,Back S,Thornberg C,et al.Local radiotherapy of exposed murine small bowel:Apoptosis and inflammation.BMC Surg 2008;8:1.
[42]Liu JJ,He H,Zhang Z,Jiang SX,Akahoshi T,Yang J,et al.Mitochondria Play a Role in the Development of Non-Apoptotic Programmed Cell Death of Neutrophils Induced by ONO-AE-248.Cell Mol Immunol 2007;4:447-53.
[43]de Waard V,Arkenbout EK,Vos M,Mocking AI,Niessen HW,Stooker W,et al.TR3 nuclear orphan receptor prevents cyclic stretch-induced proliferation of venous smooth muscle cells.Am J Pathol 2006;168:2027-35.
[44]Kishikawa H,Miura S,Yoshida H,Hirokawa M,Nakamizo H,Higuchi H,et al.Transmural pressure induces IL-6 secretion by intestinal epithelial cells.Clin Exp Immunol 2002;129:86-91.
[45]Hsieh MH,Nguyen HT.Molecular rnechanism of apoptosis induced by mechanical foroes.Int Rev Cytol 2005;245:45-90.
[46]Islam N,Haqqi TM,Jepsen KJ,Kraay M,Welter JF,Goldberg VM,et al.Hydrostatic pressure induces apoptosis in human chondrocytes from osteoarthritic cartilage through up-regulation of tumor necrosis factor-alpha,inducible nitric oxide synthase,p53,c-myc,and bax-alpha,and suppression of bcl-2.J Cell Biochem 2002;87:266-78.
[47]Attur MG,Dave M,Akamatsu M,Katoh M,Amin AR.Osteoarthritis or osteoarthrosis:the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine.Osteoarthritis Cartilage 2002;10:1-4.
[1]Coleman PJ,Scott D,Abiona A,Ashhurst DE,Mason RM,Levick JR.Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium.J Physiol 1998;509(Pt 3):695-710.
[2]Koshino T,Wada S,Ara Y,Saito T.Regeneration of degenerated articular cartilage after high tibial valgus osteotomy for medial compartmental osteoarthritis of the knee.Knee 2003;10:229-36.
[3]van der Meulen MC,Beaupre GS,Smith RL,Giddings VL,Allen WA,Athanasiou KA,et al.Fsctors influencing changes in articular cartilage following hemiarthroplasty in sheep.J Orthop Res 2002;20:669-75.
[4]Gu Z,Jin X,Feng J,Shibata T,Hu J,Zhan J,et al.Type Ⅱ collagen and aggrecan mRNA expressions in rabbit condyle following disc displacement.J Oral Rehabil 2005;32:254-9.
[5]Almarza AJ,Athanasiou KA.Effects of hydrostatic pressure on TMJ disc cells.Tissue Eng 2006;12:1285-94.
[6]Choi SH,Hwang SB.Modulation of the transforming growth factor-beta signal transduction pathway by hepatitis C virus nonstructural 5A protein.J Biol Chem 2006;281:7468-78.
[7]Huang SA,Mulcahey MA,Crescenzi A,Chung M,Kim BW,Barnes C,et al.Transforming growth factor-beta promotes inactivation of extracellular thyroid hormones via transcriptional stimulation of type 3 iodothyronine deiodinase.Mol Endocrinol 2005;19:3126-36.
[8]Shah AK,Lazatin J,Sinha RK,Lennox T,Hickok NJ,Tuan RS.Mechanism of BMP-2 stimulated adhesion of osteoblastic cells to titanium alloy.Biol Cell 1999;91:131-42.
[9]Kawakami Y,Rodriguez-Leon J,Belmonte JC.The role of TGFbetas and Sox9 during limb chondrogenesis.Curr Opin Cell Biol 2006;18:723-9.
[10]Mizuno S,Tateishi T,Ushida T,Glowacki J.Hydrostatic fluid pressure enhances matrix synthesis and accumulation by bovine chondrocytes in three-dimensional culture.J Cell Physiol 2002;193:319-27.
[11]DeLise AM,Fischer L,Tuan RS.Cellular interactions and signaling in cartilage development.Osteoarthritis Cartilage 2000;8:309-34.
[12]Darling EM,Athanasiou KA.Growth factor impact on articular cartilage subpopulations.Cell Tissue Res 2005;322:463-73.
[13]Dell'Accio F,De Bari C,El Tawil NM,Barone F,Mitsiadis TA,O'Dowd J,et al.Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury.Arthritis Res Ther 2006;8:R139.
[14]Kaarniranta K,Elo M,Sironen R,Lammi MJ,Goldring MB,Eriksson JE,et al.Hsp70 accumulation in chondrocytic cells exposed to high continuous hydrostatic pressure coincides with mRNA stabilization rather than transcriptional activation.Proc Natl Acad Sci U S A 1998;95:2319-24.
[15]Palmoski MJ,Colyer RA,Brandt KD.Joint motion in the absence of normal loading does not maintain normal articular cartilage.Arthritis Rheum 1980;23:325-34.
[16]Kiviranta I,Jurvelin J,Tammi M,Saamanen AM,Helminen HJ.Weight bearing controls glyoosaminoglycan concentration and articular cartilage thickness in the knee joints of young beagle dogs Arthritis Rheum 1987;30:801-9.
[17]Fujimura K,Kobayashi S,Suzuki T,Segami N.Histologic evaluation of temporomandibular arthritis induced by mild mechanical loading in rabbits J Oral Pathol Med 2005;34:157-63.
[18]Tanimoto K,Suzuki A,Ohno S,Honda K,Tanaka N,Doi T,et al.Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint.J Dent Res 2004;83:40-4.
[19]Perez del Palomar A,Doblare M.An accurate simulation model of anteriorly displaced TMJ discs with and without reduction.Med Eng Phys 2007;29:216-26.
[20]Kirkbride KC,Townsend TA,Bruinsma MW,Barnett JV,Blobe GC.Bone morphogenetic proteins signal through the transforming growth factor-beta type Ⅲ receptor.J Biol Chem 2008.
[21]Katagiri T,Takahashi N.Regulatory mechanisms of osteoblast and osteoclast differentiation.Oral Dis 2002;8:147-59.
[22]Csiszar A,Smith KE,Koller A,Kaley G,Edwards JG,Ungvari Z.Regulation of bone morphogenetic protein-2 expression in endothelial cells role of nuclear factor-kappaB activation by tumor necrosis factor-alpha,H2O2,and high intravascular pressure.Circulation 2005;111:2364-72.
[23]Fantozzi I,Huang W,Zhang J,Zhang S,Platoshyn O,Remillard CV,et al.Divergent effects of BMP-2 on gene expression in pulmonary artery smooth muscle cells from normal subjects and patients with idiopathic pulmonary arterial hypertension.Exp Lung Res 2005;31:783-806.
[24]Wong M,Carter DR.Articular cartilage functional histomorphology and mechanobiology:a research perspective.Bone 2003;33:1-13.
[25]Smith JD,Davies N,Willis AI,Sumpio BE,Zilla P.Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth musde cells.Endothelium 2001;8:41-8.
[26]Schild C,Trueb B.Mechanical stress is required for high-level expression of connective tissue growth factor.Exp Cell Res 2002;274:83-91.
[27]Blain EJ,Gilbert SJ,Wardale RJ,Capper SJ,Mason DJ,Duance VC.Up-regulation of matrix metalloproteinase expression and activation following cyclical compressive loading of articular cartilage in vitro.Arch Biochem Biophys 2001;396:49-55.
[28]Zhang DW,Cole SP,Deeley RG.Determinants of the substrate specificity of multidrug resistance protein 1:role of amino acid residues with hydrogen bonding potential in predicted transmembrane helix 17.J Biol Chem 2002;277:20934-41.
[29]Smith RL,Rusk SF,Ellison BE,Wessells P,Tsuchiya K,Carter DR,et al.In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure.J Orthop Res 1996;14:53-60.
[30]de Crombrugghe B,Lefebvre V,Nakashima K.Regulatory mechanisms in the pathways of cartilage and bone formation.Curr Opin Cell Biol 2001;13:721-7.
[31]Pittenger MF,Mackay AM,Beck SC,Jaiswal RK,Douglas R,Mosca JD,et al.Multilineage potential of adult human mesenchymal stem cells,Science 1999;284:143-7.
[32]Worster AA,Brower-Toland BD,Fortier LA,Bent SJ,Williams J,Nixon AJ.Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1in monolayer and insulin-like growth factor-I in a three-dimensional matrix.J Orthop Res 2001;19:738-49.
[33]Majumdar MK,Wang E,Morris EA.BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.J Cell Physiol 2001;189:275-84.
[34]Sekiya I,Colter DC,Prockop DJ.BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells.Biochem Biophys Res Commun 2001;284:411-8.
[35]Gelse K,von der Mark K,Aigner T,Park J,Schneider H.Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells.Arthritis Rheum 2003;48:430-41.
[36]Jiang J,Nicoll SB,Lu HH.Co-culture of osteoblasts and chondrocytes modulates cellular differentiation in vitro.Biochem Biophys Res Commun 2005;338:762-70.
[37]Fernandes PM.How does yeast respond to pressure? Braz J Med Biol Res 2005;38:1239-45.
[38]Shim JW,Elder SH.Influence of cyclic hydrostatic pressure on fibrocatilaginous metaplasia of achilles tendon fibroblasts.Biomech Model Mechanobiol 2006;5:247-52.
[39]Miyanishi K,Trindade MC,Lindsey DP,Beaupre GS,Carter DR,Goodman SB,et al.Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells in vitro.Tissue Eng 2006;12:2253-62.
[40]Henson FM,Vincent T.Chondrocyte outgrowth into a gelatin scaffold in a single impact load model of damage/repeir-effect of BMP-2.BMC Musculoskelet Disord 2007;8:120.
[41]Miyamoto C,Matsumoto T,Sakimura K,Shindo H.Osteogenic protein-1 with transforming growth factor-beta1:potent induce of chondrogenesis of synovial mesenchymal stem cells in vitro.J Orthop Sci 2007;12:555-61.
[42]Hanada K,Solchaga LA,Caplan AI,Hering TM,Goldberg VM,Yoo JU,et al.BMP-2 induction and TGF-beta 1 modulation of rat periosteal cell chondrogenesis.J Cell Biochem 2001;81:284-94.
[43]Soltz MA,Basalo IM,Ateshian GA.Hydrostatic pressurization and depletion of trapped lubricant pool during creep contact of a rippled indenter against a biphasic articular cartilage layer.J Biomech Eng 2003;125:585-93.
[44]Bell DM,Leung KK,Wheatley SC,Ng LJ,Zhou S,Ling KW,st al.SOX9 directly regulates the type-Ⅱ collagen gene.Nat Genet 1997;16:174-8.
[45]Finger AR,Sargent CY,Dulaney KO,Bernacki SH,Loboa EG.Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure.Tissue Eng 2007;13:1151-8.
[46]Wong M,Siegrist M,Goodwin K.Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primay chondrocytes.Bone 2003;33:685-93.
[47]Adams MA.The mechanical environment of chondrocytes in articular cartilage.Biorheology 2006;43:537-45.
[48]Voulgari PV,Papazisi D,Bai M,Zagorianakou P,Assimakopoulos D,Drosos AA.Laryngeal involvement in rheumatoid arthritis.Rheumatol Int 2005;25:321-5.
[49]Buckwalter JA.Articular cartilage injuries.Clin Orthop Relat Res 2002:21-37.
[50]Tanaka H,Murphy CL,Murphy C,Kimura M,Kawai S,Polak JM.Chondrogenic differentiation of murine embryonic stem cells.effects of culture oonditions and dexamethasone.J Cell Biochem 2004;93:454-62.
[1]Finlay GA,Thannickal VJ,Fanburg BL,Paulson KE.Transforming growth factor-beta 1-induced activation of the ERK pathway/activator protein-1 in human lung fibroblasts requires the autocrine induction of basic fibroblast growth factor.J Biol Chem 2000;275:27650-6.
[2]Stanton LA,Underhill TM,Beier F.MAP kinases in chondrocyte differentiation.Dev Biol 2003;263:165-75.
[3]Seger R,Krebs EG.The MAPK signaling cascade.FASEB J 1995;9:726-35.
[4]Hagemann C,Blank JL.The ups and downs of MEK kinase interactions.Cell Signal 2001;13:863-75.
[5]Kyriakis JM,Avruch J.Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation.Physiol Rev 2001;81:807-69.
[6]Kapur S,Baylink DJ,Lau KH.Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways.Bone 2003;32:241-51.
[7]Han Z,Boyle DL,Aupperle KR,Bennett B,Manning AM,Firestein GS.Jun N-terminal kinase in rheumatoid arthritis.J Pharmacol Exp Ther 1999;291:124-30.
[8]Murakami S,Munsta T,Ezura Y,Furuya K,Yamamoto H.Quantitative analysis of synovial fibrosis in the infrapatellar fat pad before and after anterior cruciate ligament reconstruction.Am J Sports Med 1997;25:29-34.
[9]Shull MM,Ormsby I,Kier AB,Pawlowski S,Diebold RJ,Yin M,et al.Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.Nature 1992;359:693-9.
[10]Massague J,Blain SW,Lo RS.TGFbsta signaling in growth control,cancer,and heritable disorders.Cell 2000;103:295-309.
[11]Moses HL,Yang EY,Pietenpol JA.TGF-bsta stimulation and inhibition of cell proliferation:new mechanistic insights Cell 1990;63:245-7.
[12]Border WA,Noble NA.Transforming growth factor beta in tissue fibrosis.N Engl J Med 1994;331:1286-92.
[13]Qin YX,McLeod KJ,Guilak F,Chiang FP,Rubin CT.Correlation of bony ingrowth to the distribution of stress and strain parameters surrounding a porous-coated implant.J Orthop Res 1996;14:862-70.
[14]Badorff C,Ruetten H,Mueller S,Stahmer M,Gehring D,Jung F,et al.Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces cardiac hypertrophy following pressure overload.J Clin Invest 2002;109:373-81.
[15]Su B,Karin M.Mitogen-activated protein kinase cascades and regulation of gene expression.Curr Opin Immunol 1996;8:402-11.
[16]Nishida E,Gotoh Y.The MAP kinase cascade is essential for diverse signal transduction pathways.Trends Biochem Sci 1993;18:128-31.
[17]Bardwell L.Mechanismsof MAPK signalling specificity.Biochem Soc Trans 2006;34:837-41.
[18]Sundaram MV.RTK/Ras/MAPK signaling.WormBook 2006:1-19.
[19]Hoffman LM,Weston AD,Underhill TM.Molecular mechanisms regulating chondroblast differentiation.J Bone Joint Surg Am 2003;85-A Suppl 2:124-32.
[20]Kumar A,Middleton A,Chambers TC,Mehta KD.Differential roles of extracellular signal-regulated kinase-1/2 and p38(MAPK)in interleukin-1beta- and tumor necrosis factor-alpha-inducad low density lipoprotein receptor expression in HepG2 cells.J Biol Chem 1998;273:15742-8.
[21]Singh RP,Dhawan P,Golden C,Kapoor GS,Mehta KD.One-way cross-talk between p38(MAPK)and p42/44(MAPK).Inhibition of p38(MAPK)induces low density lipoprotein receptor expression through activation of the p42/44(MAPK)cascade.J Biol Chem 1999;274:19593-600.
[22]Lai CF,Chaudhary L,Fausto A,Halstead LR,Ory DS,Avioli LV,et al.Erk is essential for growth,differentiation,integrin expression,and cell function in human osteoblastic cells J Biol Chem 2001;276:14443-50.
[23]Takeuchi Y,Suzawa M,Kikuchi T,Nishida E,Fujita T,Matsumoto T.Differentiation and transforming growth factor-beta receptor down-regulation by collagen-alpha2beta1 integrin interaction is mediated by focal adhesion kinase and its downstream signals in murine osteoblastic cells.J Biol Chem 1997;272:29309-16.
[24]Fraser D,Brunskill N,Ito T,Phillips A.Long-term exposure of proximal tubular epithelial cells to glucose induces transforming growth factor-beta 1 synthesis via an autocrine PDGF loop.Am J Pathol 2003;163:2565-74.
[25]Yoshimura H,Nakahama K,Safronova O,Tanaka N,Muneta T,Morita I.Transforming growth factor-beta stimulates IL-1beta-induced monocyte chemoattractant protein-1 expression in human synovial cells via the ERK/AP-1 pathway.Inflamm Res 2006;55:543-9.
[26]Klein-Nulend J,Roelofsen J,Semeins CM,Bronckers AL,Burger EH.Mechanical stimulation of osteopontin mRNA expression and synthesis in bone cell cultures.J Cell Physiol 1997;170:174-81.
[27]Roelofsen J,Klein-Nulend J,Burger EH.Mechanical stimulation by intermittent hydrolytic compression promotes bone-specific gene expression in vitro.J Biomech 1995;28:1493-503.
[28]Jaiswal RK,Jaiswal N,Bruder SP,Mbalaviele G,Marshak DR,Pittenger MF.Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulaed by mitogen-activated protein kinase.J Biol Chem 2000;275:9645-52.
[29]Cortizo AM,Lettieri MG,Barrio DA,Mercer N,Etcheverry SB,McCarthy AD.Advanced glycation end-products(AGEs)induce concerted changes in the osteoblastic expression of their receptor RAGE and in the activation of extracellular signal-regulated kinases(ERK).Mol Cell Biochem 2003;250:1-10.
[30]Oh CD,Chang SH,Yoon YM,Lee SJ,Lee YS,Kang SS,et al.Opposing role of mitogen-activated protein kinase subtypes,erk-1/2 and p38,in the regulation of chondrogenesis of mesenchymes.J Biol Chem 2000;275:5613-9.
[31]Adams JL,Badge AM,Kumar S,Lee JC.p38 MAP kinase:molecular target for the inhibition of pro-inflammatory cytokines.Prog Med Chem 2001;38:1-60.
[32]Schett G,Tohidast-Akrad M,Smolen JS,Schmid BJ,Steiner CW,Bitzan P,et al.Activation,differential localization,and regulation of the stress-activated protein kinases,extracellular signal-regulated kinase,c-JUN N-terminal kinase,and p38 mitogen-activated protein kinase,in synovial tissue and cells in rheumatoid arthritis.Arthritis Rheum 2000;43:2501-12.
[33]Lee DJ,Rosenfeldt H,Grinnell F.Activation of ERK and p38 MAP kinases in human fibroblasts during collagen matrix contraction.Exp Cell Res 2000;257:190-7.
[34]Wahl SM.Transforming growth factor beta the good,the bad,and the ugly.J Exp Med 1994;180:1567-90.
[35]Robinson FL,Whitehurst AW,Raman M,Cobb MH.Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1.J Biol Chem 2002;277:14844-52.
[36]Takeshita A,Chen Y,Watanabe A,Kiteno S,Hanazawa S.TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells.J Immunol 1995;155:419-26.
[37]Nanki T,Nagasaka K,Hayashida K,Saita Y,Miyasaka N.Chemokines regulate IL-6 and IL-8production by fibroblast-like synoviocytes from patients with rheumatoid arthritis.J Immunol 2001;167:5381-5.
[38]Chen W,Jin W,Cook M,Weiner HL,Wahl SM.Oral delivery of group A streptococcal cell walls augments circulating TGF-beta and suppresses streptococcal cell wall arthritis.J Immunol 1998;161:6297-304.
[39]Song XY,Gu M,Jin WW,Klinman DM,Wahl SM.Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.J Clin Invest 1998;101:2615-21.
[40]Massague J,Wotton D.Transcriptional control by the TGF-beta/Smad signaling system.EMBO J 2000;19:1745-54.
[41]Yamaguchi K,Shirakabe K,Shibuya H,Irie K,Oishi I,Ueno N,et al.Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction.Science 1995;270:2008-11.
[42]Yu L,Hebert MC,Zhang YE.TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses.EMBO J 2002;21:3749-59.
[43]Zavadil J,Bitzer M,Liang D,Yang YC,Massimi A,Kneitz S,et al.Genetic programs of epithelial dell plasticity directed by transforming growth factor-beta.Proc Natl Acad Sci U S A 2001;98:6686-91.
[44]Alessi DR,Cuenda A,Cohen P,Dudley DT,Saltiel AR.PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo.J Biol Chem 1995;270:27489-94.
[45]Lee SW,Choi KY,Cho JY,Jung SH,Song KB,Park EK,et al.TGF-beta2 stimulates cranial suture closure through activation of the Erk-MAPK pathway.J Cell Biochem 2006;98:981-91.
[1]Sambajon VV,Cillo JE,Jr.,Gassner RJ,Buckley MJ.The effects of mechanical strain on synovial fibroblasts.J Oral Maxillofac Surg 2003;61:707-12.
[2]Chiquet M,Renedo AS,Huber F,Fluck M.How do fibroblasts translate mechanical signals into changes in extracellular matrix production? Matrix Biol 2003;22:73-80.
[3]Gynther GW,Dijkgraaf LC,Reinholt FP,Holmlund AB,Liem RS,de Bont LG.Synovial inflammation in arthroscopically obtained biopsy specimens from the temporomandibular joint:a review of the literature and a proposed histologic grading system.J Oral Maxillofac Surg 1998;56:1281-6;discussion 7.
[4]Dijkgraaf LC,Liem RS,van der Weele LT,de Bont LG.Correlation between arthroscopically observed changes and synovial light microscopic findings in osteoarthritic temporomandibular joints.Int J Oral Maxillofac Surg 1999;28:83-9.
[5]Gynther GW,Holmlund AB,Reinholt FP.Synovitis in internal derangement of the temporomandibular joint:correlation between arthroscopic and histologic findings.J Oral Maxillofac Surg 1994;52:913-7;discussion 8.
[6]姜潇.牡丹皮药理作用的研究进展.中国新医药 2004;3:110-1.
[7]Li Y,Zhang W,Huang L,Shi J.[Pharmacological of cortex moutan and core].Zhongguo Zhong Yao Za Zhi 1997;22:214-6,54.
[8]吴少华,马云保.罗晓东.丹皮的化学成分研究.中草药 2002;33:679-80.
[9]Matsuda H,Ohta T,Kawaguchi A,Yoshikawa M.Bioactive constituents of chinese natural medicines.Ⅵ.Mouten cortex.(2):structures and radical scavenging effects of suffruticosides A,B,C,D,and E and galloyl-oxypaeoniflorin.Chem Pharm Bull(Tokyo)2001;49:69-72.
[10]Rho S,Chung HS,Kang M,Lee E,Cho C,Kim H,et al.Inhibition of production of reactive oxygen species and gene expression profile by treatment of ethanol extract of moutan cortex radicis in oxidative stressed PC12 cells.Biol Pharm Bull 2005;28:661-6.
[11]Zheng YQ,We W.Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes.Int Immunopharmacol 2005;5:1560-73.
[12]Kamimura D,Ishihara K,Hirano T.IL-6 signal transduction and its physiological roles:the signal orchestration model.Rev Physiol Biochem Pharmacol 2003;149:1-38.
[13]Okuda Y,Bardin CW,Hodgskin LR,Morris PL.Interleukins-1 alpha and -1 beta regulate interleukin-6 expression in Leydig and Sertoli cells.Recent Prog Horm Res 1995;50:367-72.
[14]Ogura N,Tobe M,Sakamaki H,Kujiraoka H,Akiba M,Abiko Y,et al.Interleukin-1 beta induces interleukin-6 mRNA expression and protein production in synovial cells from human temporomandibular joint.J Oral Pathol Med 2002;31:353-60.
[15]Kawai Y,Kubota E,Okabe E.Reactive oxygen species participation in experimentally induced arthritis of the temporomandibular joint in rats.J Dent Res 2000;79:1489-95.
[16]Kubota E,Kubota T,Matsumoto J,Shibata T,Murakami KI.Synovial fluid cytokines and proteinases as markers of temporomandibular joint disease.J Oral Maxillofac Surg 1998;56:192-8.
[17]Kubota E,Imamura H,Kubota T,Shibata T,Murakami K.Interleukin 1 beta and stromelysin (MMP3)activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint.J Oral Maxillofac Surg 1997;55:20-7;discussion 7-8.
[18]Sandler NA,Buckley MJ,Cillo JE,Braun TW.Correlation of inflammatory cytokines with arthroscopic findings in patients with temporomandibular joint internal derangements.J Oral Maxillofac Surg 1998;56:534-43;discussion 43-4.
[19]Brown RD,Jones GM,Laird RE,Hudson P,Long CS.Cytokines regulate matrix metalloproteinases and migration in cardiac fibroblasts.Biochem Biophys Res Commun 2007;362:200-5.
[20]Ahmed S,Anuntiyo J,Malemud CJ,Haqqi TM.Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis:a review.Evid Based Complement Alternat Med 2005;2:301-8.
[21]Genfa L,Jiang Z,Hong Z,Yimin Z,Liangxi W,Guo W,et al.The screening and isolation of an effective anti-endotoxin monomer from Radix Paeoniae Rubra using affinity biosensor technology.Int Immunopharmacol 2005;5:1007-17.
[22]Frondoza CG,Sohrabi A,Polotsky A,Phan PV,Hungerford DS,Lindmark L.An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using human synoviocyte cultures.In Vitro Cell Dev Biol Anim 2004;40:95-101.
[23]Kim SH,Kim SA,Park MK,Kim SH,Park YD,Na HJ,et al.Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-alpha.Int Immunopharmacol 2004;4:279-87.
[24]Chou TC.Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia Br J Pharmacol 2003;139:1146-52.
[25]Chun S-C,Jee SY,Lee SG,Park SJ,Lee JR,Kim SC.Anti-Inflammatory Activity of the Methanol Extract of Moutan Cortex in LPS-Activated Raw264.7 Cells.eCAM 2006:nel093.
[26]Tohda C,Nakayama N,Hatanaka F,Komatsu K.Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes:A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.Evid Based Complement Alternat Med 2006;3:255-60.
[27]Lin Y,Pape HD,Friedrich R.Use of superoxide dismutase(SOD)in patients with temporomandibular joint dysfunction--a preliminary study.Int J Oral Maxillofac Surg 1994;23:428-9.
[28]Alpaslan GH,Alpaslan C.Efficacy of temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate in treatment of internal derangemants.J Oral Maxillofac Surg 2001;59:613-8;discussion 8-9.
[29]Zhang G,Yu Z,Zhao H.[Protective effect of paeonol on repeated cerebral ischemia in rats].Zhong Yao Cai 1997;20:626-8.
[30]Lee SE,Hwang HJ,Ha JS,Jeong HS,Kim JH.Screening of medicinal plant extracts for antioxidant activity.Life Sci 2003;73:167-79.
[1]A.Heath C,R.Magari S.Mini-review:Mechanical factors affecting cartilage regeneration in vitro.Biotechnology and Bioengineering 1996;50:430-7.
[2]You L,Temiyasathit S,Lee P,Kim CH,Tummala P,Yao W,et al.Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading.Bone 2008;42:172-9.
[3]Setton LA,Chen J.Mechanobiology of the intervertebral disc and relevance to disc degeneration.J Bone Joint Surg Am 2006;88 Suppl 2:52-7.
[4]Muller S,Labrador V,Dalsla N,Dumas D,Sun R,Wang X,et al.From hemorheology to vascular mechanobiology:An overview.Clin Hemorheol Microcirc 2004;30:185-200.
[5]Kappagoda CT,Ravi K.The rapidly adapting receptors in mammalian airways and their responses to changes in extravascular fluid volume Exp Physiol 2006;91:647-54.
[6]Angele P,Yoo JU,Smith C,Mansour J,Jepsen KJ,Nerlich M,et al.Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro.J Orthop Res 2003;21:451-7.
[7]Martin JS,Brown LS,Haberstroh KM.Microfilaments are involved in renal cell responses to sustained hydrostatic pressure.J Urol 2005;173:1410-7.
[8]Walboomers XF,Elder SE,Bumgardner JD,Jansen JA.Hydrodynamic compression of young and adult rat osteoblast-like cells on titanium fiber mesh.J Biomed Mater Res A 2006;76:16-24.
[9]Barzegar-Jalali M,A dibkia K,Mohammadi G,Zeraati M,Bolagh BA,Nokhodchi A.Propranolol hydrochloride osmotic capsule with controlled onset of release.Drug Deliv 2007;14:461-8.
[10]Ingber DE.Cellular mechanotransduction:putting all the pieces together again.FASEB J 2006;20:811-27.
[11]Sato S,Goto S,Nasu F,Motegi K.Natural course of disc displacement with reduction of the temporomandibular joint:changes in clinical signs and symptoms.J Oral Maxillofac Surg 2003;61:32-4.
[12]Shung KK,Krisko BA,Ballard JO,3rd.Acoustic measurement of erythrocyte compressibility.J Acoust Soc Am 1982;72:1364-7.
[13]Myers KA,Rattner JB,Shrive NG,Hart DA.Hydrostatic pressure sensation in cells:integration into the tensegrity model.Biochem Cell Biol 2007;85:543-51.
[14]Charras GT,Horton MA.Single cell mechanotransduction and its modulation analyzed by atomic force microscope indentation.Biophys J 2002;82:2970-81.
[15]Moosavi-Nejad SF,Hosseni SH,Satoh M,Takayama K.Shock wave induced cytoskeletal and morphological deformations in a human renal carcinoma cell line.Cancer Sci 2006;97:296-304.
[16]Csizmadia V,Raczynski A,Csizmadia E,Fedyk ER,Rottman J,Alden CL.Effect of an experimental proteasome inhibitor on the cytoskeleton,cytosolic protein turnover,and induction in the neuronal cells in vitro.Neurotoxicology 2007.
[17]Schewkunow V,Sharma KP,Diez G,Klemm AH,Sharma PC,Goldmann WH.Thermodynamic evidence of non-muscle myosin Ⅱ-lipid-membrane interaction.Biochem Biophys Res Commun 2008;366:500-5.
[18]Jortikka MO,Parkkinen JJ,Inkinen RI,Karner J,Jarvelainen HT,Nelimarkka LO,et al.The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure.Arch Biochem Biophys 2000;374:172-80.
[19]Frey B,Franz S,Sheriff A,Korn A,Bluemelhuber G,Gaipl US,et al.Hydrostatic pressure induced death of mammalian cells engages pathways related to apoptosis or necrosis.Cell Mol Biol (Noisy-le-grand)2004;50:459-67.
[20]Lammi MJ,Elo MA,Sironen RK,Karjalainen HM,Kaarniranta K,Helminen HJ.Hydrostatic pressure-induced changes in cellular protein synthesis.Biorheology 2004;41:309-13.
[21]Hirsch C,Gauss R,Sommer T.Coping with stress:cellular relaxation techniques.Trends Cell Biol 2006;16:657-63.
[22]Ferreira ST,De Felice FG,Chapeaurouge A.Metastable,partially folded states in the productive folding and in the misfolding and amyloid aggregation of proteins.Cell Biochem Biophys 2006;44:539-48.
[23]Fioravanti A,Moretti E,Scapigliati G Cervone R,Galeazzi M,Collodel G.Morphological,immunocytochemical and biochemical studies in human osteoarthritic chondrocytes exposed to IL-1b and cyclical hydrostatic pressure Clin Exp Rheumatol 2007;25:690-5.
[24]Ishihara H,McNally DS,Urban JP,Hall AC.Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk.J Appl Physiol 1996;80:839-46.
[25]Tesevski V,Sorbetti JM,Chiu SS,Shrive NG,Hart DA.Influence of mechanical and biological signals on gene expression in human MG-63 cells:evidence for a conplex interplay between hydrostatic compression and vitamin D3 or TGF-beta1 on MMP-1 and MMP-3 mRNA levels.Biochem Cell Biol 2005;83:96-107.
[26]Evans CE,Mylchreest S,Andrew JG.Age of donor alters the effect of cyclic hydrostatic pressure on production by human macrophages and osteoblasts of sRANKL,OPG and RANK.BMC Musculoskelet Disord 2006;7:21.
[27]Roelofsen J,Klein-Nulend J,Burger EH.Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro.J Biomech 1995;28:1493-503.
[28]Del Pozo-Insfran D,Del Follo-Martinez A,Talcott ST,Brenes CH.Stability of copigmented anthocyanins and ascorbic acid in muscadine grape juice processed by high hydrestatic pressure.J Food Sci 2007;72:S247-53.
[29]Muir R Sample SJ,Barrett JG,McCarthy J,Vanderby R,Jr.,Markel MD,et al.Effect of fatigue loading and associated matrix microdamage on bone blood flow and interstitial fluid flow.Bone 2007;40:948-56.
[30]Freed LE,Vunjsk-Novakovic G,Marquis JC,Langer R.Kinetics of chondrocyte growth in cell-polymer implants.Biotechnol Bioeng 1994;43:597-604.
[31]Jin G,Sah RL,Li YS,Lotz M,Shyy JY,Chien S.Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes.J Orthop Res 2000;18:899-908.
[32]Lee MS,Trindade MC,Ikenoue T,Schurman DJ,Goodman SB,Smith RL.Effects of shear stress on nitric oxide and matrix protein gene expression in human osteoarthritic chondrocytes in vitro.J Orthop Res 2002;20:556-61.
[33]Palmoski M,Perricone E,Brandt KD.Development and reversal of a proteoglycan aggregation defect in normal canine knee cartilage after immobilization.Arthritis Rheum 1979;22:508-17.
[34]van Kampen GP,Veldhuijzen JP,Kuijer R,van de Stadt RJ,Schipper CA.Cartilage response to mechanical force in high-density chondrocyte cultures.Arthritis Rheum 1985;28:419-24.
[35]Veldhuijzen JP,Huisman AH,Vermeiden JP,Prahl-Andersen B.The growth of cartilage cells in vitro and the effect of intermittent compressive force.A histological evaluation.Connect Tissue Res 1987;16:187-96.
[35]Parkkinen JJ,Ikonen J,Lammi MJ,Laakkonen J,Tammi M,Helminen HJ.Effects of cyclic hydrostatic pressure on proteoglycan synthesis in cultured chondrocytes and articular cartilage explants.Arch Biochem Biophys 1993;300:458-65.
[37]Magari SM.In vitro growth of articular cartilage on a polymer subjected to low levels of intermittent compressive force,Hanover,NH,USA.:Dartmouth College,,1994.
[38]Mizuno S.A novel method for assessing effects of hydrostatic fluid pressure on intracellular calcium:a study with bovine articular chondrocytes.Am J Physiol Cell Physiol 2005;288:C329-37.
[39]Neufeld AH,Liu B.Comparison of the signal transduction pathways for the induction of gene expression of nitric oxide synthase-2 in response to two different stimuli.Nitric Oxide 2003;8:95-102.
[40]Wu HC,Wang TW,Kang PL,Tsuang YH,Sun JS,Lin FH.Coculture of endothelial and smooth muscle cells on a collagen membrane in the development of a small-diameter vascular graft.Biomaterials 2006.
[41]Duwel P,Jungling E,Westhofen M,Luckhoff A.Potassium currents in vestibular type Ⅱ hair cells activated by hydrostatic pressure.Neuroscience 2003;116:963-72.
[42]Salvador-Silva M,Aoi S,Parker A,Yang P,Pecen P,Hernandez MR.Responses and signaling pathways in human optic nerve head astrocytes exposed to hydrostatic pressure in vitro.Glia 2004;45:364-77.
[43]van Oort B,van Hoek A,Ruban AV,van Amerongen H.Equilibrium between quenched and nonquenched conformations of the major plant light-harvesting complex studied with high-pressure time-resolved fluorescence.J Phys Chem B 2007;111:7631-7.
[44]Staves MP.Cytoplasmic streeming and gravity sensing in Chara internodal cells.Planta 1997;203:S79-84.
[45]Cooper ST,Maxwell AL,Kizana E,Ghoddusi M,Hardeman EC,Alexander IE,eL al.C2C12co-culture on a fibroblast substratum enables sustained survival of contractile,highly differentiated myotubes with peripheral nuclei and adult fast myosin expression.Cell Motil Cytoskeleton 2004;58:200-11.
[46]Martinac B.Mechanosensitive ion channels:molecules of mechanotransduction.J Cell Sci 2004;117:2449-60.
[47]Norvell SM,Alvarez M,Bidwell JR,Pavalko FM.Fluid shear stress induces beta-catenin signaling in osteoblasts.Calcif Tissue Int 2004;75:396-404.
[48]Knight MM,Toyoda T,Lee DA,Bader DL.Mechanical compression and hydrostatic pressure induce recersible changes in actin cytoskeletal organisation in chondrocytes in agarose.J Biomech 2006;39:1547-51.
[49]Ayesh EE,Jensen TS,Svensson P.Hypersensitivity to mechanical and intra-articular electrical stimuli in persons with painful temporomandibular joints.J Dent Res 2007;86:1187-92.
[50]Kurz B,Jin M,Patwari P,Cheng DM,Lark MW,Grodzinsky AJ.Biosynthetic response and mechanical properties of articular cartilage after injurious compression.J Orthop Res 2001;19:1140-6.
[51]May B,Saha S,Saltzman M.A three-dimensional mathematical model of temporomandibular joint loading.Clin Biomech(Bristol,Avon)2001;16:489-95.
[52]Tanaka E,Kawai N,Tanaka M,Todoh M,van Eijden T,Hanaoka K,et al.The frictional coefficient of the temporomandibular joint and its dependency on the magnitude and duration of joint loading.J Dent Res 2004;83:404-7.
[53]Sharawy M,All AM,Choi WS.Experimental induction of anterior disk displacement of the rabbit craniomandibular joint:an immuno-electron microscopic study of collagen and proteoglycan occurrence in the condylar cartilage.J Oral Pathol Med 2003;32:176-84.
[54]Franchi M,Trire A,Quaranta M,Orsini E,Ottani V.Collagen structure of tendon relates to function.ScientificWorldJournal 2007;7:404-20.
[55]Schroeder Y,Sivan S,Wilson W,Merkher Y,Huyghe JM,Maroudas A,et al.Are disc pressure,stress,and osmolarity affected by intra- and extrafibrillar fluid exchange? J Orthop Res 2007;25:1317-24.
[56]Tanaka E,Yamano E,Dalla-Bona DA,Watanabe M,Inubushi T,Shirakura M,et al.Dynamic compressive properties of the mandibular condylar cartilage.J Dent Res 2006;85:571-5.
[57]Tanaka E,van Eijden T.Biomechanical behavior of the temporomandibular joint disc.Crit Rev Oral Biol Med 2003;14:138-50.
[58]Hu K,Radhakrishnan P,Patel RV,Mao JJ.Regional structural and viscoelastic properties of fibrocartilage upon dynamic nanoindentation of the articular condyle.J Struct Biol 2001;136:46-52.
[59]Satir P,Chdstensen ST.Overview of structure and function of mammalian cilia.Annu Rev Physiol 2007;69:377-400.
[60]Smith RL,Carter DR,Schurman DJ.Pressure and shear differentially alter human articular chondrocyte metabolism:a review.Clin Orthop Relat Res 2004:S89-95.