膝骨关节炎软骨组织中内质网应激对炎症分子、骨代谢分子分泌的影响
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摘要
目的:研究膝骨关节炎(OA)软骨组织中内质网应激对炎症分子、骨代谢分子分泌的影响。方法:选择2013年6月～2017年2月期间因膝骨关节炎在本院接受关节置换术的患者56例作为OA组,同期因外伤在我院接受膝关节置换术的患者40例作为对照组。手术中收集关节软骨组织并测定内质网应激基因的表达水平、炎症及骨代谢分子的分泌量。结果:OA组关节软骨中蛋白激酶R样内质网激酶(PERK)、肌醇必需酶1(IRE1)、活化转录因子6(ATF6)、CCAAT/增强子结合蛋白同源蛋白(CHOP)、含半胱氨酸的天冬氨酸蛋白水解酶-12(caspase-12)的mRNA表达水平以及白细胞介素-1β(IL-1β)、IL-6、CXC趋化因子配体12(CXCL12)、趋化素(Chemerin)、人类软骨糖蛋白-39(YKL-40)、基质金属蛋白酶13(MMP13)、核因子κB受体活化因子配体(RANKL)的分泌量明显高于对照组,骨保护素(OPG)、骨钙素(OC)、胶原蛋白-I(COL-I)、COL-Ⅲ的分泌量明显低于对照组且PERK、IRE1、ATF6、CHOP、Caspase-12的mRNA表达水平与IL-1β、IL-6、CXCL12、Chemerin、YKL-40、MMP13、RANKL呈正相关,与OPG、OC、COL-I、COL-Ⅲ呈负相关。结论:膝OA软骨组织中内质网应激的过度激活与炎症反应激活、骨代谢紊乱有关。
Objective: To study the effects of endoplasmic reticulum stress in cartilage tissue of knee osteoarthritis(OA) on the secretion of inflammatory molecules and bone metabolism molecules. Methods: The patients who received joint replacement in our hospital due to knee osteoarthritis between June 2013 and February 2017 were enrolled as the OA group, and the patients who received knee replacement in our hospital due to trauma during the same period were enrolled as the control group. During the operation, articular cartilage tissue was collected to measure the expression of endoplasmic reticulum stress genes as well as the secretion of inflammatory molecules and bone metabolism molecules. Results: PRKR-like endoplasmic reticulum kinase(PERK), inositol-requiring enzyme 1(IRE1), activating transcription factor 6(ATF6), CCAAT/enhancer-binding protein homologous protein(CHOP), cysteinyl aspartate specific proteinase-12(caspase-12) mRNA expression as well as interleukin-1β(IL-1β), IL-6, CXC chemokine ligand 12(CXCL12), Chemerin, human cartilage glycoprotein-39(YKL-40), matrix metalloproteinase 13(MMP13) and receptor activator for nuclear factor-κ B ligand(RANKL) secretion in articular cartilage of OA group were obviously higher than those of control group whereas osteoprotegerin(OPG), osteocalcin(OC), collagen-I(COL-I) and COL-Ⅲ secretion were obviously lower than those of control group, and PERK, IRE1, ATF6, CHOP and Caspase-12 mRNA expression were positively correlated with IL-1β, IL-6, CXCL12, Chemerin, YKL-40, MMP13 and RANKL, and negatively correlated with OPG, OC, COL-I and COL-Ⅲ. Conclusion: The over-activation of endoplasmic reticulum stress in knee OA cartilage tissue is related to the inflammatory response activation and bone metabolism disorder.
Objective: To study the effects of endoplasmic reticulum stress in cartilage tissue of knee osteoarthritis(OA) on the secretion of inflammatory molecules and bone metabolism molecules. Methods: The patients who received joint replacement in our hospital due to knee osteoarthritis between June 2013 and February 2017 were enrolled as the OA group, and the patients who received knee replacement in our hospital due to trauma during the same period were enrolled as the control group. During the operation, articular cartilage tissue was collected to measure the expression of endoplasmic reticulum stress genes as well as the secretion of inflammatory molecules and bone metabolism molecules. Results: PRKR-like endoplasmic reticulum kinase(PERK), inositol-requiring enzyme 1(IRE1), activating transcription factor 6(ATF6), CCAAT/enhancer-binding protein homologous protein(CHOP), cysteinyl aspartate specific proteinase-12(caspase-12) mRNA expression as well as interleukin-1β(IL-1β), IL-6, CXC chemokine ligand 12(CXCL12), Chemerin, human cartilage glycoprotein-39(YKL-40), matrix metalloproteinase 13(MMP13) and receptor activator for nuclear factor-κ B ligand(RANKL) secretion in articular cartilage of OA group were obviously higher than those of control group whereas osteoprotegerin(OPG), osteocalcin(OC), collagen-I(COL-I) and COL-Ⅲ secretion were obviously lower than those of control group, and PERK, IRE1, ATF6, CHOP and Caspase-12 mRNA expression were positively correlated with IL-1β, IL-6, CXCL12, Chemerin, YKL-40, MMP13 and RANKL, and negatively correlated with OPG, OC, COL-I and COL-Ⅲ. Conclusion: The over-activation of endoplasmic reticulum stress in knee OA cartilage tissue is related to the inflammatory response activation and bone metabolism disorder.
引文
1 Mobasheri A,Rayman MP,Gualillo O,et al.The role of metabolism in the pathogenesis of osteoarthritis[J].Nat Rev Rheumatol,2017,13(5):302-311.
2 柏茂盛,赵建宁,洪叶.脂代谢与骨代谢信号通路及与骨代谢相关疾病的关系:理论进展与热点方向[J].中国组织工程研究,2018,22(20):3269-3274.
3 Chin KY.The spice for joint inflammation:anti-inflammatory role of curcumin in treating osteoarthritis[J].Drug Des Devel Ther,2016,20(10):3029-3042.
4 吴浩,孟志超,曹永平,等.内质网应激对膝骨关节炎大鼠关节软骨细胞的影响[J].中国组织工程研究,2017,21(16):2502-2508.
5 中华医学会骨科学分会.骨关节炎诊治指南(2007年版)[J].中国临床医生杂志,2008,36(1):28-30.
6 熊飞,韦宜山.内质网应激与软骨细胞凋亡[J].中国组织工程研究,2017,21(36):5886-5891.
7 刘超,夏长所,李晓飞,等.活性氧激活内质网诱导软骨细胞凋亡的研究[J].中华临床医师杂志(电子版),2017,11(4):591-595.
8 李川.Toll 样受体4与白细胞介素1β在膝骨关节炎中的表达意义[J].中华关节外科杂志(电子版),2017,11(1):64-67.
9 Li X,Ren W,Xiao ZY,et al.GACAT3 promoted proliferation of osteoarthritis synoviocytes by IL-6/STAT3 signaling pathway[J].Eur Rev Med Pharmacol Sci,2018,22(16):5114-5120.
10 ?im?ek Kaya G,Yap1c1 Yavuz G,K1z1ltun? A.Expression of chemerin in the synovial fluid of patients with temporomandibular joint disorders[J].J Oral Rehabil,2018,45(4):289-294.
11 杨赞礼,刘俊波,黄武斌,等.血浆和关节液趋化因子12的表达水平与膝骨关节炎严重程度的相关性[J].广东医学,2017,38(4):571-573.
12 苏晓恩,孔志强,朱娟,等.膝关节骨关节炎软骨中YKL-40、IL-1β的表达及相关性探讨[J].重庆医学,2017,46(4):480-482.
13 肖壮,唐涛,朱成华,等.破骨细胞在骨关节炎中的增殖变化及意义[J].重庆医学,2017,46(30):4181-4184.
14 Cassuto J,Folestad A,G?thlin J,et al.The key role of proinflammatory cytokines,matrix proteins,RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients[J].Bone,2018,107:66-77.
15 Bonato LL,Quinelato V,Borojevic R,et al.Haplotypes of the RANK and OPG genes are associated with chronic arthralgia in individuals with and without temporomandibular disorders[J].Int J Oral Maxillofac Surg,2017,46(9):1121-1129.
16 Wang G,Bu X,Zhang Y,et al.LncRNA-UCA1 enhances MMP-13 expression by inhibiting miR-204-5p in human chondrocytes[J].Oncotarget,2017,8(53):91281-91290.
17 Noh KC,Park SH,Yang CJ,et al.Involvement of synovial matrix degradation and angiogenesis in oxidative stress-exposed degenerative rotator cuff tears with osteoarthritis[J].J Shoulder Elbow Surg,2018,27(1):141-150.
2 柏茂盛,赵建宁,洪叶.脂代谢与骨代谢信号通路及与骨代谢相关疾病的关系:理论进展与热点方向[J].中国组织工程研究,2018,22(20):3269-3274.
3 Chin KY.The spice for joint inflammation:anti-inflammatory role of curcumin in treating osteoarthritis[J].Drug Des Devel Ther,2016,20(10):3029-3042.
4 吴浩,孟志超,曹永平,等.内质网应激对膝骨关节炎大鼠关节软骨细胞的影响[J].中国组织工程研究,2017,21(16):2502-2508.
5 中华医学会骨科学分会.骨关节炎诊治指南(2007年版)[J].中国临床医生杂志,2008,36(1):28-30.
6 熊飞,韦宜山.内质网应激与软骨细胞凋亡[J].中国组织工程研究,2017,21(36):5886-5891.
7 刘超,夏长所,李晓飞,等.活性氧激活内质网诱导软骨细胞凋亡的研究[J].中华临床医师杂志(电子版),2017,11(4):591-595.
8 李川.Toll 样受体4与白细胞介素1β在膝骨关节炎中的表达意义[J].中华关节外科杂志(电子版),2017,11(1):64-67.
9 Li X,Ren W,Xiao ZY,et al.GACAT3 promoted proliferation of osteoarthritis synoviocytes by IL-6/STAT3 signaling pathway[J].Eur Rev Med Pharmacol Sci,2018,22(16):5114-5120.
10 ?im?ek Kaya G,Yap1c1 Yavuz G,K1z1ltun? A.Expression of chemerin in the synovial fluid of patients with temporomandibular joint disorders[J].J Oral Rehabil,2018,45(4):289-294.
11 杨赞礼,刘俊波,黄武斌,等.血浆和关节液趋化因子12的表达水平与膝骨关节炎严重程度的相关性[J].广东医学,2017,38(4):571-573.
12 苏晓恩,孔志强,朱娟,等.膝关节骨关节炎软骨中YKL-40、IL-1β的表达及相关性探讨[J].重庆医学,2017,46(4):480-482.
13 肖壮,唐涛,朱成华,等.破骨细胞在骨关节炎中的增殖变化及意义[J].重庆医学,2017,46(30):4181-4184.
14 Cassuto J,Folestad A,G?thlin J,et al.The key role of proinflammatory cytokines,matrix proteins,RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients[J].Bone,2018,107:66-77.
15 Bonato LL,Quinelato V,Borojevic R,et al.Haplotypes of the RANK and OPG genes are associated with chronic arthralgia in individuals with and without temporomandibular disorders[J].Int J Oral Maxillofac Surg,2017,46(9):1121-1129.
16 Wang G,Bu X,Zhang Y,et al.LncRNA-UCA1 enhances MMP-13 expression by inhibiting miR-204-5p in human chondrocytes[J].Oncotarget,2017,8(53):91281-91290.
17 Noh KC,Park SH,Yang CJ,et al.Involvement of synovial matrix degradation and angiogenesis in oxidative stress-exposed degenerative rotator cuff tears with osteoarthritis[J].J Shoulder Elbow Surg,2018,27(1):141-150.