破骨细胞功能相关分子CTSK与ClC-7的临床及基础研究
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摘要
骨改建是维持骨骼质量、强度以及钙盐平衡必不可少的过程,是破骨细胞介导的骨吸收过程和成骨细胞介导的骨形成过程协同作用的结果。一旦破骨细胞与成骨细胞之间的平衡被打破将会导致骨形态和结构的异常,从而引发一系列骨代谢性疾病。近年来随着细胞生物学及分子遗传学等学科的发展,破骨细胞在遗传性骨病中的作用逐渐被揭开。有研究表明:电压门控氯离子通道7(voltage-gated chloride channel 7 gene,CLCN7)及组织蛋白酶K(cathepsin K,CTSK)等十余个基因异常均可引起破骨细胞功能障碍,进而导致遗传性骨硬化性疾病。本研究选择了3例CTSK或CLCN7基因突变所致的遗传性骨病患者进行相关的临床和基础研究,旨在探讨破骨细胞功能相关分子CTSK与ClC-7参与疾病发生的机理,为相关疾病的诊断、预防及治疗提供理论依据。
CTSK基因突变所致致密性成骨不全的临床和基础研究
作为破骨细胞重要的功能分子,CTSK主要参与降解骨有机基质,并可以通过调控破骨细胞凋亡控制破骨细胞数量。CTSK基因突变将导致一类罕见的常染色体隐性遗传性疾病——致密性成骨不全。本研究对1996年以来文献报道的109个家系中的159例致密性成骨不全患者进行了回顾性研究,结果发现:①其中59个家系(涉及104例患者)的基因分析发现了33种不同的CTSK基因突变类型,主要以错义突变为主(69.70%),且位于6号外显子的Arg241和位于7号外显子的Ala277是突变的高发位点;59个家系中除了1个单亲二倍体家系外,携带纯合子突变的家系共44个(74.58%),携带复合杂合子突变的家系为14个(23.73%)。②根据74个家系中97例致密性成骨不全患者的临床表征,本研究发现身材矮小、骨密度增高、颅缝不闭合、颅骨膨隆、频发骨折、下颌角变钝、颌骨发育不良、四肢短小伴指/趾端溶骨是该病最常见的八大表征。③除了错义突变患者指/趾端溶骨和下颌角变钝阳性率较高外(P<0.05),其余基因型与表型之间没有明确的关系。根据回顾性研究的结果,我们首次创建了CTSK基因突变数据库(http://www.centralmutations.org/Lsdb.php#CTSK)。
为了进一步研究CTSK功能,探讨CTSK参与疾病发生的机理,本部分研究选择了我科接诊的一例致密性成骨不全患者,在全面检查、基因分析和家系研究的基础上不但证实了该患者的诊断(该患者30年来一直被诊断为骨硬化症),还发现了一对新的CTSK杂合突变位点(p.Trp29X和p.Tyr283Cys)、2个父系p.Tyr283Cys携带者和7个母系p.Trp29X携带者。同时提出颅颌面部特征在致密性成骨不全的鉴别诊断中具有重要意义。
对该患者接受死骨清除术时一并去除的左侧上颌磨牙进行Micro CT扫描和组织学观察,结果发现:牙根周围牙骨质明显增厚(平均厚度为1.30±0.42 mm),牙骨质与周围牙槽骨之间没有明确的界限,根管狭窄伴部分钙化闭锁,但牙本质无明显异常。从而提出CTSK除了在骨代谢方面发挥重要作用外,很可能参与牙骨质的形成并发挥重要作用。同时提出了致密性成骨不全患者拔牙后继发颌骨骨髓炎的一个可能机制:增厚的牙骨质与周围牙槽骨之间没有明确的界限,使得拔牙时容易损伤患牙周围的牙槽骨,增大拔牙创面,造成更多的牙槽骨暴露,从而导致拔牙后继发颌骨骨髓炎的风险增大。
免疫功能相关研究发现该患者外周血总IgE和抑制性T淋巴细胞升高、IL-17A水平和辅助性T淋巴细胞降低。利用白芍总甙胶囊和胸腺肽肠溶胶囊进行免疫调节治疗12周后,各项异常的免疫指标均有不同程度的改善,且右侧上颌骨骨髓炎相关的临床症状逐渐缓解,口内病灶区新生肉芽组织形成并逐渐增大,部分覆盖拔牙创底。该患者外周血IL-17A水平降低不仅预示着CTSK可能在人免疫系统中发挥重要作用,同时也揭示了致密性成骨不全患者拔牙后继发颌骨骨髓炎的又一可能机制:辅助性T淋巴细胞17及其相关细胞因子的匮乏导致致密性成骨不全患者抵抗外源微生物感染的能力减低,从而增加拔牙后颌骨骨髓炎发生的风险。
CLCN7基因突变所致骨硬化症的临床和基础研究
ClC-7作为一种Cl-/H+反向转运体位于破骨细胞的褶皱缘上,通过控制氯离子通透性,调控骨吸收陷窝内的pH值。CLCN7基因突变将导致一组遗传性疾病——骨硬化症,根据其遗传方式、临床特征、疾病的发病年龄以及严重程度,可以分为三型:常染色体隐性遗传性骨硬化症(autosomal recessive osteopetrosis,ARO)、常染色体显性遗传性骨硬化症Ⅱ型(autosomal dominant osteopetrosis typeⅡ,ADOⅡ)、中间型常染色体隐性遗传性骨硬化症(intermediate autosomal recessive osteopetrosis,IARO)。本部分研究选择2例不同类型的CLCN7基因突变导致的骨硬化症患者进行了相关的临床和基础研究。
通过详细的临床研究和CLCN7基因测序分析,证实了病例2为中国首例IARO患者,并发现了一个新的CLCN7纯合突变位点p.Pro470Leu,其母为该位点的杂合携带者。同时发现该患者表现有睾丸及阴茎发育障碍,染色体核型分析发现其Y染色体增大(Yq+)。在以往的研究中,并未见骨硬化症患者表现有生殖系统发育障碍的报道。但CLCN7基因突变、Yq+和男性外生殖器发育障碍之间是否存在相关性还有待于进一步研究。
CLCN7基因测序分析,明确了病例3为CLCN7基因杂合突变(p.Arg286Trp)导致的ADOⅡ。外周血免疫球蛋白、IL-17水平及淋巴细胞亚型分析发现该患者外周血辅助性T淋巴细胞轻度降低,余未见明显异常。ClC-7在人免疫系统中的作用还有待于进一步研究。
本部分研究还发现病例2、3均表现有部分后牙埋藏伴不同程度的牙根发育障碍,于是首次提出ClC-7可能参与牙根发育,且其在牙根发育中的作用存在时空效应和剂量效应的假设。
结论
本研究通过对159例致密性成骨不全患者的文献回顾性研究,得出了致密性成骨不全的临床及分子遗传学特征,并首次创建了CTSK基因突变数据库。通过对3例CTSK或CLCN7基因突变所致的遗传性骨病患者进行相关研究,发现CTSK很可能在人类免疫系统和牙骨质发育方面发挥重要作用,并首次提出ClC-7参与牙根发育,且其在牙根发育中的作用存在时空效应和剂量效应的假设。
Bone remodelling is an essential process in maintaining bone quality and strength, as well as calcium homeostasis. Remodelling is a cycle of bone resorption by osteoclasts and formation of new bone by osteoblasts. Break of the balance between osteoclasts and osteoblasts will lead to abnormal formation and structure of bone, and then cause a series of bone metabolic disease. In recent years, as the development of cell biology and molecular genetics, the role of osteoclasts in genetic bone disease became clearing. Some studies have shown that more than ten genes, including the voltage-gated chloride channel 7 (CLCN7) and cathepsin K (CTSK), can cause osteoclast dysfunction, which lead to genetic osteosclerosis disease. In order to investigate the role of CTSK and ClC-7 in related disease, provide theoretical basis for the diagnosis, prevention and treatment of related diseases, this study selected three cases caused by CTSK or CLCN7 mutations and did some clinical and basic research.
Research on CTSK and pycnodysostosis
In osteoclasts, CTSK is responsible for degradation of bone matrix proteins, and may also act as a potential regulator of apoptosis and senescence, controlling osteoclast numbers. Mutations in the CTSK gene cause a rare autosomal recessive bone disorder called pycnodysostosis. Here we performed a literature retrospective study of 159 pycnodysostosis patients reported since 1996 and found that 33 different CTSK mutations have been found in 59 unrelated pycnodysostosis families. A total of 69.70% of the mutations are missense mutations. The hot mutation spots are found in exons 6 and 7. Short stature, increased bone density, open fontanels and sutures, frontal and parietal bossing, pathologic fractures, obtuse mandibular angle, hypoplasia of jaws, and stubby hands and feet with osteolysis of the distal phalanges are the top eight phenotypes of pycnodysostosis. For the first time, we constructed an online database, which listed all published CTSK mutations since 1996 (http://www.centralmutations.org/Lsdb.php#CTSK).
Based on the study of a pycnodysostosis family, the proband of which was misdiagnosed as osteopetrosis for 30 years, we revealed novel compound heterozygous mutations of CTSK gene (p.Trp29X and p.Tyr283Cys), and highlighted the role of oral and craniofacial examinations in the diagnosis of pycnodysostosis. Additionally, for the first time, we used micro CT scanning and histological analysis to reveal the dental characteristic in the patient with pycnodysostosis, and proposed that disappearance of the boundary between cementum and alveolar bone may lead to post extraction osteomyelitis. Immunologic investigation of the patient showed a significantly reduced level of IL-17A in serum and a decreased ratio of helper/suppressor T lymphocytes. Immunotherapy using thymic peptides plus total glucosides of white peony improved immune homeostasis and clinical manifestations of maxillary osteomyelitis. This result indicated that CTSK may play an important role in human immune system and attenuated function of Th 17 cells may be involved in the pathogenesis of osteomyelitis in pycnodysostosis patients.
Research on ClC-7 and osteopetrosis
ClC-7 is a Cl-/H+ antiporter, that it constitutes the major Cl- permeability of osteoclasts, and that it is important in acidification in the resorption pit. Mutations in the CLCN7 gene cause osteopetrosis, which is a heterogeneous group of genetic disorders. Based on its severity, age of onset and means of inheritance, osteopetrosis is classified into three forms: autosomal recessive osteopetrosis (ARO), autosomal dominant osteopetrosis type II (ADO II), and intermediate autosomal recessive osteopetrosis (IARO). In this part, we selected 2 cases caused by CLCN7 mutations and did some clinical and basic research. One patient is the first IARO patient in China with a novel homozygous variant in CLCN7 gene (p.Pro470Leu) and the other is an ADO II patient with a reported heterozygous variant in CLCN7 gene (p.Arg286Trp). The impressive clinical features of these two osteopetrosis patients are root hypoplasia and unerupted tooth germs beside the generally increased bone intensity. We supposed that ClC-7 in tooth cells may contribute directly to the root formation, and its role may depend on position and quantity.
Conclusions
In this study, we performed a literature retrospective study of 159 pycnodysostosis patients and found the genetic characteristics of CTSK mutations and the clinical phenotypes of pycnodysostosis. We constructed an online database, which listed all published CTSK mutations since 1996. Based on the research on three cases caused by CTSK or CLCN7 mutations, we found that CTSK might play an important role in human immune system and cementum formation. Moreover, we suppose that ClC-7 in different tooth cells may contribute directly to the root formation, and its role may depend on position and quantity.
CTSK基因突变所致致密性成骨不全的临床和基础研究
作为破骨细胞重要的功能分子,CTSK主要参与降解骨有机基质,并可以通过调控破骨细胞凋亡控制破骨细胞数量。CTSK基因突变将导致一类罕见的常染色体隐性遗传性疾病——致密性成骨不全。本研究对1996年以来文献报道的109个家系中的159例致密性成骨不全患者进行了回顾性研究,结果发现:①其中59个家系(涉及104例患者)的基因分析发现了33种不同的CTSK基因突变类型,主要以错义突变为主(69.70%),且位于6号外显子的Arg241和位于7号外显子的Ala277是突变的高发位点;59个家系中除了1个单亲二倍体家系外,携带纯合子突变的家系共44个(74.58%),携带复合杂合子突变的家系为14个(23.73%)。②根据74个家系中97例致密性成骨不全患者的临床表征,本研究发现身材矮小、骨密度增高、颅缝不闭合、颅骨膨隆、频发骨折、下颌角变钝、颌骨发育不良、四肢短小伴指/趾端溶骨是该病最常见的八大表征。③除了错义突变患者指/趾端溶骨和下颌角变钝阳性率较高外(P<0.05),其余基因型与表型之间没有明确的关系。根据回顾性研究的结果,我们首次创建了CTSK基因突变数据库(http://www.centralmutations.org/Lsdb.php#CTSK)。
为了进一步研究CTSK功能,探讨CTSK参与疾病发生的机理,本部分研究选择了我科接诊的一例致密性成骨不全患者,在全面检查、基因分析和家系研究的基础上不但证实了该患者的诊断(该患者30年来一直被诊断为骨硬化症),还发现了一对新的CTSK杂合突变位点(p.Trp29X和p.Tyr283Cys)、2个父系p.Tyr283Cys携带者和7个母系p.Trp29X携带者。同时提出颅颌面部特征在致密性成骨不全的鉴别诊断中具有重要意义。
对该患者接受死骨清除术时一并去除的左侧上颌磨牙进行Micro CT扫描和组织学观察,结果发现:牙根周围牙骨质明显增厚(平均厚度为1.30±0.42 mm),牙骨质与周围牙槽骨之间没有明确的界限,根管狭窄伴部分钙化闭锁,但牙本质无明显异常。从而提出CTSK除了在骨代谢方面发挥重要作用外,很可能参与牙骨质的形成并发挥重要作用。同时提出了致密性成骨不全患者拔牙后继发颌骨骨髓炎的一个可能机制:增厚的牙骨质与周围牙槽骨之间没有明确的界限,使得拔牙时容易损伤患牙周围的牙槽骨,增大拔牙创面,造成更多的牙槽骨暴露,从而导致拔牙后继发颌骨骨髓炎的风险增大。
免疫功能相关研究发现该患者外周血总IgE和抑制性T淋巴细胞升高、IL-17A水平和辅助性T淋巴细胞降低。利用白芍总甙胶囊和胸腺肽肠溶胶囊进行免疫调节治疗12周后,各项异常的免疫指标均有不同程度的改善,且右侧上颌骨骨髓炎相关的临床症状逐渐缓解,口内病灶区新生肉芽组织形成并逐渐增大,部分覆盖拔牙创底。该患者外周血IL-17A水平降低不仅预示着CTSK可能在人免疫系统中发挥重要作用,同时也揭示了致密性成骨不全患者拔牙后继发颌骨骨髓炎的又一可能机制:辅助性T淋巴细胞17及其相关细胞因子的匮乏导致致密性成骨不全患者抵抗外源微生物感染的能力减低,从而增加拔牙后颌骨骨髓炎发生的风险。
CLCN7基因突变所致骨硬化症的临床和基础研究
ClC-7作为一种Cl-/H+反向转运体位于破骨细胞的褶皱缘上,通过控制氯离子通透性,调控骨吸收陷窝内的pH值。CLCN7基因突变将导致一组遗传性疾病——骨硬化症,根据其遗传方式、临床特征、疾病的发病年龄以及严重程度,可以分为三型:常染色体隐性遗传性骨硬化症(autosomal recessive osteopetrosis,ARO)、常染色体显性遗传性骨硬化症Ⅱ型(autosomal dominant osteopetrosis typeⅡ,ADOⅡ)、中间型常染色体隐性遗传性骨硬化症(intermediate autosomal recessive osteopetrosis,IARO)。本部分研究选择2例不同类型的CLCN7基因突变导致的骨硬化症患者进行了相关的临床和基础研究。
通过详细的临床研究和CLCN7基因测序分析,证实了病例2为中国首例IARO患者,并发现了一个新的CLCN7纯合突变位点p.Pro470Leu,其母为该位点的杂合携带者。同时发现该患者表现有睾丸及阴茎发育障碍,染色体核型分析发现其Y染色体增大(Yq+)。在以往的研究中,并未见骨硬化症患者表现有生殖系统发育障碍的报道。但CLCN7基因突变、Yq+和男性外生殖器发育障碍之间是否存在相关性还有待于进一步研究。
CLCN7基因测序分析,明确了病例3为CLCN7基因杂合突变(p.Arg286Trp)导致的ADOⅡ。外周血免疫球蛋白、IL-17水平及淋巴细胞亚型分析发现该患者外周血辅助性T淋巴细胞轻度降低,余未见明显异常。ClC-7在人免疫系统中的作用还有待于进一步研究。
本部分研究还发现病例2、3均表现有部分后牙埋藏伴不同程度的牙根发育障碍,于是首次提出ClC-7可能参与牙根发育,且其在牙根发育中的作用存在时空效应和剂量效应的假设。
结论
本研究通过对159例致密性成骨不全患者的文献回顾性研究,得出了致密性成骨不全的临床及分子遗传学特征,并首次创建了CTSK基因突变数据库。通过对3例CTSK或CLCN7基因突变所致的遗传性骨病患者进行相关研究,发现CTSK很可能在人类免疫系统和牙骨质发育方面发挥重要作用,并首次提出ClC-7参与牙根发育,且其在牙根发育中的作用存在时空效应和剂量效应的假设。
Bone remodelling is an essential process in maintaining bone quality and strength, as well as calcium homeostasis. Remodelling is a cycle of bone resorption by osteoclasts and formation of new bone by osteoblasts. Break of the balance between osteoclasts and osteoblasts will lead to abnormal formation and structure of bone, and then cause a series of bone metabolic disease. In recent years, as the development of cell biology and molecular genetics, the role of osteoclasts in genetic bone disease became clearing. Some studies have shown that more than ten genes, including the voltage-gated chloride channel 7 (CLCN7) and cathepsin K (CTSK), can cause osteoclast dysfunction, which lead to genetic osteosclerosis disease. In order to investigate the role of CTSK and ClC-7 in related disease, provide theoretical basis for the diagnosis, prevention and treatment of related diseases, this study selected three cases caused by CTSK or CLCN7 mutations and did some clinical and basic research.
Research on CTSK and pycnodysostosis
In osteoclasts, CTSK is responsible for degradation of bone matrix proteins, and may also act as a potential regulator of apoptosis and senescence, controlling osteoclast numbers. Mutations in the CTSK gene cause a rare autosomal recessive bone disorder called pycnodysostosis. Here we performed a literature retrospective study of 159 pycnodysostosis patients reported since 1996 and found that 33 different CTSK mutations have been found in 59 unrelated pycnodysostosis families. A total of 69.70% of the mutations are missense mutations. The hot mutation spots are found in exons 6 and 7. Short stature, increased bone density, open fontanels and sutures, frontal and parietal bossing, pathologic fractures, obtuse mandibular angle, hypoplasia of jaws, and stubby hands and feet with osteolysis of the distal phalanges are the top eight phenotypes of pycnodysostosis. For the first time, we constructed an online database, which listed all published CTSK mutations since 1996 (http://www.centralmutations.org/Lsdb.php#CTSK).
Based on the study of a pycnodysostosis family, the proband of which was misdiagnosed as osteopetrosis for 30 years, we revealed novel compound heterozygous mutations of CTSK gene (p.Trp29X and p.Tyr283Cys), and highlighted the role of oral and craniofacial examinations in the diagnosis of pycnodysostosis. Additionally, for the first time, we used micro CT scanning and histological analysis to reveal the dental characteristic in the patient with pycnodysostosis, and proposed that disappearance of the boundary between cementum and alveolar bone may lead to post extraction osteomyelitis. Immunologic investigation of the patient showed a significantly reduced level of IL-17A in serum and a decreased ratio of helper/suppressor T lymphocytes. Immunotherapy using thymic peptides plus total glucosides of white peony improved immune homeostasis and clinical manifestations of maxillary osteomyelitis. This result indicated that CTSK may play an important role in human immune system and attenuated function of Th 17 cells may be involved in the pathogenesis of osteomyelitis in pycnodysostosis patients.
Research on ClC-7 and osteopetrosis
ClC-7 is a Cl-/H+ antiporter, that it constitutes the major Cl- permeability of osteoclasts, and that it is important in acidification in the resorption pit. Mutations in the CLCN7 gene cause osteopetrosis, which is a heterogeneous group of genetic disorders. Based on its severity, age of onset and means of inheritance, osteopetrosis is classified into three forms: autosomal recessive osteopetrosis (ARO), autosomal dominant osteopetrosis type II (ADO II), and intermediate autosomal recessive osteopetrosis (IARO). In this part, we selected 2 cases caused by CLCN7 mutations and did some clinical and basic research. One patient is the first IARO patient in China with a novel homozygous variant in CLCN7 gene (p.Pro470Leu) and the other is an ADO II patient with a reported heterozygous variant in CLCN7 gene (p.Arg286Trp). The impressive clinical features of these two osteopetrosis patients are root hypoplasia and unerupted tooth germs beside the generally increased bone intensity. We supposed that ClC-7 in tooth cells may contribute directly to the root formation, and its role may depend on position and quantity.
Conclusions
In this study, we performed a literature retrospective study of 159 pycnodysostosis patients and found the genetic characteristics of CTSK mutations and the clinical phenotypes of pycnodysostosis. We constructed an online database, which listed all published CTSK mutations since 1996. Based on the research on three cases caused by CTSK or CLCN7 mutations, we found that CTSK might play an important role in human immune system and cementum formation. Moreover, we suppose that ClC-7 in different tooth cells may contribute directly to the root formation, and its role may depend on position and quantity.
引文
1. Seeman, E. and P.D. Delmas, Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med, 2006. 354(21): p. 2250-61.
2. Noble, B., Bone microdamage and cell apoptosis. Eur Cell Mater, 2003. 6: p. 46-55.
3. Burr, D.B., Targeted and nontargeted remodeling. Bone, 2002. 30(1): p. 2-4.
4. Parfitt, A.M., Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone, 2002. 30(1): p. 5-7.
5. Takahashi, H., B. Epker, and H.M. Frost, Resorption Precedes Formative Activity. Surg Forum, 1964. 15: p. 437-8.
6. Hattner, R., B.N. Epker, and H.M. Frost, Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature, 1965. 206(983): p. 489-90.
7. Martin, T.J., Hormones in the coupling of bone resorption and formation. Osteoporos Int, 1993. 3 Suppl 1: p. 121-5.
8. Martin, T.J. and N.A. Sims, Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med, 2005. 11(2): p. 76-81.
9. Roodman, G.D., Cell biology of the osteoclast. Exp Hematol, 1999. 27(8): p. 1229-41.
10. Tatsumi, S., et al., Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab, 2007. 5(6): p. 464-75.
11. Dodds, R.A., et al., Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces: an in vitro and ex vivo study of remodeling bone. J Bone Miner Res, 1995. 10(11): p. 1666-80.
12. Everts, V., et al., The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res, 2002. 17(1): p. 77-90.
13. Mulari, M.T., et al., Osteoblast-like cells complete osteoclastic bone resorption and form new mineralized bone matrix in vitro. Calcif Tissue Int, 2004. 75(3): p. 253-61.
14. Tran Van, P., A. Vignery, and R. Baron, An electron-microscopic study of the bone-remodeling sequence in the rat. Cell Tissue Res, 1982. 225(2): p. 283-92.
15. Huffer, W.E., Morphology and biochemistry of bone remodeling: possible control by vitamin D, parathyroid hormone, and other substances. Lab Invest, 1988. 59(4): p. 418-42.
16. Martin, T.J. and E. Seeman, New mechanisms and targets in the treatment of bone fragility. Clin Sci (Lond), 2007. 112(2): p. 77-91.
17. Segovia-Silvestre, T., et al., Advances in osteoclast biology resulting from the study of osteopetrotic mutations. Hum Genet, 2009. 124(6): p. 561-77.
18. Marks, S.C., Jr. and D.G. Walker, The hematogenous origin of osteoclasts: experimental evidence from osteopetrotic (microphthalmic) mice treated with spleen cells from beige mouse donors. Am J Anat, 1981. 161(1): p. 1-10.
19. Roodman, G.D., Regulation of osteoclast differentiation. Ann N Y Acad Sci, 2006. 1068: p. 100-9.
20. Helfrich, M.H., R.H. Mieremet, and C.W. Thesingh, Osteoclast formation in vitro from progenitor cells present in the adult mouse circulation. J Bone Miner Res, 1989. 4(3): p. 325-34.
21. Thesingh, C.W., Formation sites and distribution of osteoclast progenitor cells during the ontogeny of the mouse. Dev Biol, 1986. 117(1): p. 127-34.
22. Chalhoub, N., et al., Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human. Nat Med, 2003. 9(4): p. 399-406.
23. Findlay, D.M. and T.J. Martin, Receptors of calciotropic hormones. Horm Metab Res, 1997. 29(3): p. 128-34.
24. Frattini, A., et al., Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet, 2000. 25(3): p. 343-6.
25. Gelb, B.D., et al., Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science, 1996. 273(5279): p. 1236-8.
26. Hayman, A.R., et al., Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis. Development, 1996. 122(10): p. 3151-62.
27. Kornak, U., et al., Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell, 2001. 104(2): p. 205-15.
28. Sly, W.S., et al., Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci U S A, 1983. 80(9): p. 2752-6.
29. Vu, T.H., et al., MMP-9/gelatinase B is a key regulator of growth plateangiogenesis and apoptosis of hypertrophic chondrocytes. Cell, 1998. 93(3): p. 411-22.
30. Del Fattore, A., A. Cappariello, and A. Teti, Genetics, pathogenesis and complications of osteopetrosis. Bone, 2008. 42(1): p. 19-29.
31. Boyle, W.J., W.S. Simonet, and D.L. Lacey, Osteoclast differentiation and activation. Nature, 2003. 423(6937): p. 337-42.
32. Wiktor-Jedrzejczak, W., et al., Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci U S A, 1990. 87(12): p. 4828-32.
33. Arai, F., et al., Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med, 1999. 190(12): p. 1741-54.
34. Lacey, D.L., et al., Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell, 1998. 93(2): p. 165-76.
35. Li, J., et al., RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A, 2000. 97(4): p. 1566-71.
36. Simonet, W.S., et al., Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell, 1997. 89(2): p. 309-19.
37. Yasuda, H., et al., Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology, 1998. 139(3): p. 1329-37.
38. Eghbali-Fatourechi, G., et al., Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest, 2003. 111(8): p. 1221-30.
39. Helfrich, M.H., Osteoclast diseases and dental abnormalities. Arch Oral Biol, 2005. 50(2): p. 115-22.
40. Stenbeck, G., Formation and function of the ruffled border in osteoclasts. Semin Cell Dev Biol, 2002. 13(4): p. 285-92.
41. Li, Y.P., et al., Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nat Genet, 1999. 23(4): p. 447-51.
42. Kornak, U., et al., Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Hum Mol Genet, 2000. 9(13): p. 2059-63.
43. Scimeca, J.C., et al., The gene encoding the mouse homologue of the human osteoclast-specific 116-kDa V-ATPase subunit bears a deletion in osteosclerotic (oc/oc) mutants. Bone, 2000. 26(3): p. 207-13.
44. Blair, H.C., et al., Osteoclastic bone resorption by a polarized vacuolar proton pump. Science, 1989. 245(4920): p. 855-7.
45. Blair, H.C., et al., Passive chloride permeability charge coupled to H(+)-ATPase of avian osteoclast ruffled membrane. Am J Physiol, 1991. 260(6 Pt 1): p. C1315-24.
46. Henriksen, K., et al., Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am J Pathol, 2004. 164(5): p. 1537-45.
47. Karsdal, M.A., et al., Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am J Pathol, 2005. 166(2): p. 467-76.
48. Baron, R., et al., Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization ofa 100-kD lysosomal membrane protein at the osteoclast ruffled border. J Cell Biol, 1985. 101(6): p. 2210-22.
49. Tolar, J., S.L. Teitelbaum, and P.J. Orchard, Osteopetrosis. N Engl J Med, 2004. 351(27): p. 2839-49.
50. Teti, A., et al., Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts. J Clin Invest, 1989. 83(1): p. 227-33.
51. Jansen, I.D., et al., Ae2(a,b)-deficient mice exhibit osteopetrosis of long bones but not of calvaria. FASEB J, 2009. 23(10): p. 3470-81.
52. Bossard, M.J., et al., Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem, 1996. 271(21): p. 12517-24.
53. Saftig, P., et al., Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A, 1998. 95(23): p. 13453-8.
54. Gowen, M., et al., Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res, 1999. 14(10): p. 1654-63.
55. Nishi, Y., et al., Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res, 1999. 14(11): p. 1902-8.
56. Henriksen, K., et al., Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification. J Bone Miner Res, 2006. 21(1): p. 58-66.
57. Nesbitt, S.A. and M.A. Horton, Trafficking of matrix collagens through bone-resorbing osteoclasts. Science, 1997. 276(5310): p. 266-9.
58. Salo, J., et al., Removal of osteoclast bone resorption products bytranscytosis. Science, 1997. 276(5310): p. 270-3.
59. Jentsch, T.J., CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Crit Rev Biochem Mol Biol, 2008. 43(1): p. 3-36.
60. Zhao, Q., et al., CLC-7: a potential therapeutic target for the treatment of osteoporosis and neurodegeneration. Biochem Biophys Res Commun, 2009. 384(3): p. 277-9.
61. Kida, Y., et al., Localization of mouse CLC-6 and CLC-7 mRNA and their functional complementation of yeast CLC gene mutant. Histochem Cell Biol, 2001. 115(3): p. 189-94.
62.殷丽天等,氯离子通道CIC家族的结构特点与功能研究.山西医科大学学报, 2006. 37(1): p.100-2.
63. Fukuda, M., Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem, 1991. 266(32): p. 21327-30.
64. Eskelinen, E.L., Y. Tanaka, and P. Saftig, At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol, 2003. 13(3): p. 137-45.
65. Lange, P.F., et al., ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature, 2006. 440(7081): p. 220-3.
66. Graves, A.R., et al., The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes. Nature, 2008. 453(7196): p. 788-92.
67. Kasper, D., et al., Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J, 2005. 24(5): p. 1079-91.
68. Jentsch, T.J., I. Neagoe, and O. Scheel, CLC chloride channels andtransporters. Curr Opin Neurobiol, 2005. 15(3): p. 319-25.
69. Frattini, A., et al., Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res, 2003. 18(10): p. 1740-7.
70. Berdowska, I., Cysteine proteases as disease markers. Clinica Chimica Acta, 2004. 342(1-2): p. 41-69.
71. LaLonde, J.M., et al., The crystal structure of human procathepsin K. Biochemistry, 1999. 38(3): p. 862-9.
72. Schilling, A.F., et al., High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin K. Osteoporos Int, 2007. 18(5): p. 659-69.
73. Donnarumma, M., et al., Molecular analysis and characterization of nine novel CTSK mutations in twelve patients affected by pycnodysostosis. Mutation in brief #961. Online. Hum Mutat, 2007. 28(5): p. 524.
74. Hou, W.S., et al., Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis. J Clin Invest, 1999. 103(5): p. 731-8.
75. Sivaraman, J., et al., Crystal structure of wild-type human procathepsin K. Protein Sci, 1999. 8(2): p. 283-90.
76. McQueney, M.S., et al., Autocatalytic activation of human cathepsin K. J Biol Chem, 1997. 272(21): p. 13955-60.
77. Turk, B., V. Turk, and D. Turk, Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol Chem, 1997. 378(3-4): p. 141-50.
78. Mujawar, Q., et al., Pycnodysostosis with unusual findings: a case report.Cases J, 2009. 2: p. 6544.
79. Lecaille, F., D. Bromme, and G. Lalmanach, Biochemical properties and regulation of cathepsin K activity. Biochimie, 2008. 90(2): p. 208-26.
80. Podgorski, I., Future of anticathepsin K drugs: dual therapy for skeletal disease and atherosclerosis? Future Med Chem, 2009. 1(1): p. 21-34.
81. Bromme, D. and J. Kaleta, Thiol-dependent cathepsins: pathophysiological implications and recent advances in inhibitor design. Curr Pharm Des, 2002. 8(18): p. 1639-58.
82. Chen, W., et al., Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence. Hum Mol Genet, 2007. 16(4): p. 410-23.
83. Alibhai, Z.A., et al., Presentation and management of chronic osteomyelitis in an African patient with pycnodysostosis. Oral Dis, 1999. 5(1): p. 87-9.
84. Karkabi, S., et al., Pyknodysostosis: imaging and laboratory observations. Calcif Tissue Int, 1993. 53(3): p. 170-3.
85. Gowen, M., et al., Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res, 1999. 14(10): p. 1654-63.
86. Asagiri, M., et al., Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science, 2008. 319(5863): p. 624-7.
87. Liu, J., et al., Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol, 2004. 24(8): p. 1359-66.
88. Lutgens, S.P., et al., Cathepsin cysteine proteases in cardiovascular disease. FASEB J, 2007. 21(12): p. 3029-41.
89. Balemans, W., L. Van Wesenbeeck, and W. Van Hul, A clinical andmolecular overview of the human osteopetroses. Calcif Tissue Int, 2005. 77(5): p. 263-74.
90. Vernejoul, M.-C.d., A. Schulz, and M. Uwe Kornak, PhD, CLCN7-Related Osteopetrosis. [http://www.ncbi.nlm.nih.gov/books/NBK1127/]
91. Nii, A., et al., Mild osteopetrosis in the microphthalmia-oak ridge mouse. A model for intermediate autosomal recessive osteopetrosis in humans. Am J Pathol, 1995. 147(6): p. 1871-82.
92. Campos-Xavier, A.B., et al., Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis. Hum Genet, 2003. 112(2): p. 186-9.
93. Rysavy, M., K.P. Arun, and A. Wozniak, Fracture treatment in intermediate autosomal recessive osteopetrosis. Orthopedics, 2007. 30(7): p. 577-80.
94. Selby, P.L., et al., Guidelines on the management of Paget's disease of bone. Bone, 2002. 31(3): p. 366-73.
95. Scarsbrook, A., M. Brown, and D. Wilson, UK guidelines on management of Paget's disease of bone. Rheumatology (Oxford), 2004. 43(3): p. 399-400.
96. Takata, S., et al., Guidelines for diagnosis and management of Paget's disease of bone in Japan. J Bone Miner Metab, 2006. 24(5): p. 359-67.
97. Cundy, T., et al., A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet, 2002. 11(18): p. 2119-27.
98. Nakatsuka, K., Y. Nishizawa, and S.H. Ralston, Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bpduplication in the TNFRSF11A gene. J Bone Miner Res, 2003. 18(8): p. 1381-5.
99. Whyte, M.P., et al., Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease. J Bone Miner Res, 2000. 15(12): p. 2330-44.
100.Wallace, R.G., et al., Familial expansile osteolysis. Clin Orthop Relat Res, 1989(248): p. 265-77.
101. Fleming, K.W., G. Barest, and O. Sakai, Dental and facial bone abnormalities in pyknodysostosis: CT findings. AJNR Am J Neuroradiol, 2007. 28(1): p. 132-4.
102. Naeem, M., S. Sheikh, and W. Ahmad, A mutation in CTSK gene in an autosomal recessive pycnodysostosis family of Pakistani origin. BMC Med Genet, 2009. 10: p. 76.
103. Gelb, B.D., J.G. Edelson, and R.J. Desnick, Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping. Nat Genet, 1995. 10(2): p. 235-7.
104. Gelb, B.D., et al., Cathepsin K: isolation and characterization of the murine cDNA and genomic sequence, the homologue of the human pycnodysostosis gene. Biochem Mol Med, 1996. 59(2): p. 200-6.
105. Polymeropoulos, M.H., et al., The gene for pycnodysostosis maps to human chromosome 1cen-q21. Nat Genet, 1995. 10(2): p. 238-9.
106. Rothenbuhler, A., et al., Near normalization of adult height and body proportions by growth hormone in pycnodysostosis. J Clin Endocrinol Metab, 2010. 95(6): p. 2827-31.
107. Osimani, S., et al., Craniosynostosis: A rare complication of pycnodysostosis. Eur J Med Genet, 2010. 53(2): p. 89-92.
108. Laffranchi, L., et al., Use of CBCT in the orthodontic diagnosis of apatient with pycnodysostosis. Minerva Stomatol, 2010. 59(11-12): p. 653-61.
109. Khan, B., Z. Ahmed, and W. Ahmad, A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosis. J Investig Med, 2010. 58(5): p. 720-4.
110. Bertola, D., et al., Craniosynostosis in pycnodysostosis: broadening the spectrum of the cranial flat bone abnormalities. Am J Med Genet A, 2010. 152A(10): p. 2599-603.
111. Li, H.Y., et al., Molecular analysis of a novel cathepsin K gene mutation in a Chinese child with pycnodysostosis. J Int Med Res, 2009. 37(1): p. 264-9.
112. Chavassieux, P., et al., Mechanisms of the anabolic effects of teriparatide on bone: insight from the treatment of a patient with pycnodysostosis. J Bone Miner Res, 2008. 23(7): p. 1076-83.
113. Fratzl-Zelman, N., et al., Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J Clin Endocrinol Metab, 2004. 89(4): p. 1538-47.
114. Everts, V., et al., Cathepsin K deficiency in pycnodysostosis results in accumulation of non-digested phagocytosed collagen in fibroblasts. Calcif Tissue Int, 2003. 73(4): p. 380-6.
115. Fujita, Y., et al., Novel mutations of the cathepsin K gene in patients with pycnodysostosis and their characterization. J Clin Endocrinol Metab, 2000. 85(1): p. 425-31.
116. Haagerup, A., et al., Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population. Eur J Hum Genet, 2000. 8(6): p. 431-6.
117. Ho, N., et al., Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein. J Bone Miner Res, 1999. 14(10): p. 1649-53.
118. Nishi, Y., et al., Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res, 1999. 14(11): p. 1902-8.
119. Gelb, B.D., et al., Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis. Am J Hum Genet, 1998. 62(4): p. 848-54.
120. Johnson, M.R., et al., A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis. Genome Res, 1996. 6(11): p. 1050-5.
121. Gelb, B.D., et al., Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science, 1996. 273(5279): p. 1236-8.
122. Toral-Lopez, J., et al., Familial Pycnodysostosis: Identification of a Novel Mutation in the CTSK Gene (Cathepsin K). J Investig Med, 2011. 59(2):277-80.
123. Darcan, S., et al., A case of pycnodysostosis with growth hormone deficiency. Clin Genet, 1996. 50(5): p. 422-5.
124. Schmitz, J.P., et al., Mandibular reconstruction in a patient with pyknodysostosis. J Oral Maxillofac Surg, 1996. 54(4): p. 513-7.
125. Soliman, A.T., et al., Defective growth hormone secretion in children with pycnodysostosis and improved linear growth after growth hormone treatment. Arch Dis Child, 1996. 75(3): p. 242-4.
126. Mocan, H., et al., Pyknodysostosis: hemangioma of the skull as a new finding. Genet Couns, 1997. 8(3): p. 213-6.
127. Hunt, N.P., et al., The dental, craniofacial, and biochemical features of pyknodysostosis: a report of three new cases. J Oral Maxillofac Surg, 1998. 56(4): p. 497-504.
128. O'Connell, A.C., M.T. Brennan, and C.A. Francomano, Pycnodysostosis: orofacial manifestations in two pediatric patients. Pediatr Dent, 1998. 20(3): p. 204-7.
129. Agarwal, I., C. Kirubakaran, and G. Sridhar, Pyknodysostosis: a report of two siblings with unusual manifestations. Ann Trop Paediatr, 1999. 19(3): p. 301-5.
130. Bathi, R.J. and V.N. Masur, Pyknodysostosis--a report of two cases with a brief review of the literature. Int J Oral Maxillofac Surg, 2000. 29(6): p. 439-42.
131. Landa, S., et al., Maxillofacial alterations in a family with pycnodysostosis. Med Oral, 2000. 5(3): p. 169-176.
132. Thomas, N., et al., Association of central giant-cell granuloma of the maxilla with pyknodysostosis. Br J Oral Maxillofac Surg, 2000. 38(2): p. 159-60.
133. Kirita, T., et al., 2010-7-18 Mandibular reconstruction using a vascularised fibula osteocutaneous flap in a patient with pyknodysostosis. Br J Plast Surg, 2001. 54(8): p. 712-4.
134. Soliman, A.T., et al., Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. Metabolism, 2001. 50(8): p. 905-11.
135. Ram, P.B., S.K. Ram, and H. Neitzschman, Radiology case of the month. Sclerotic bone disease in an 8-year-old dwarf. Pycnodysostosis. J La State Med Soc, 2002. 154(6): p. 287-8.
136. Zenke, M.S., et al., Pycnodysostosis associated with spondylolysis. Arch Orthop Trauma Surg, 2002. 122(4): p. 248-50.
137. Karakurt, L., et al., Pycnodysostosis associated with bilateral congenital pseudarthrosis of the clavicle. Arch Orthop Trauma Surg, 2003. 123(2-3): p. 125-7.
138. Kundu, Z.S., et al., Subtrochanteric fracture managed by intramedullary nail in a patient with pycnodysostosis. Joint Bone Spine, 2004. 71(2): p. 154-6.
139. Norholt, S.E., J.Bjerregaard, and L. Mosekilde, Maxillary distraction osteogenesis in a patient with pycnodysostosis: a case report. J Oral Maxillofac Surg, 2004. 62(8): p. 1037-40.
140. Singh, A.R., et al., Pyknodysostosis: visceral manifestations and simian crease. Indian J Pediatr, 2004. 71(5): p. 453-5.
141. Kato, H., et al., Mandibular osteomyelitis and fracture successfully treated with vascularised iliac bone graft in a patient with pycnodysostosis. Br J Plast Surg, 2005. 58(2): p. 263-6.
142. Muto, T., et al., Pharyngeal narrowing as a common feature in pycnodysostosis--a cephalometric study. Int J Oral Maxillofac Surg, 2005. 34(6): p. 680-5.
143. Moniz, N., et al., Mandibular reconstruction with autogenous graft in patient presenting pyknodysostosis: case report. J Oral Maxillofac Surg, 2006. 64(8): p. 1292-5.
144. Wadia, F., N. Shah, and M. Porter, Bilateral charnley low-friction arthroplasty with cement in a patient with pyknodysostosis. A case report. J Bone Joint Surg Am, 2006. 88(8): p. 1846-8.
145. Dimitrakopoulos, I., C. Magopoulos, and T. Katopodi, MandibularOsteomyelitis in a Patient With Pyknodysostosis: A Case Report of a
50-Year Misdiagnosis. J Oral Maxillofac Surg 2007. 65(3): p. 580-585.
146. Fonteles, C.S., et al., Cephalometric characteristics and dentofacial abnormalities of pycnodysostosis: report of four cases from Brazil. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2007. 104(4): p. e83-90.
147. Nakase, T., et al., Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis. Arch Orthop Trauma Surg, 2007. 127(3): p. 161-5.
148. Ainola, M., et al., Erosive arthritis in a patient with pycnodysostosis: an experiment of nature. Arthritis Rheum, 2008. 58(11): p. 3394-401.
149. Alves Pereira, D., L. Berini Aytes, and C. Gay Escoda, Pycnodysostosis. A report of 3 clinical cases. Med Oral Patol Oral Cir Bucal, 2008. 13(10): p. e633-5.
150. F., S.L., et al., Pyknodysostosis: Oral ?ndings and differential diagnosis. J Indian Soc Pedod Prevent Dent 2008. Supplement: p. S23-S25.
151. Olubaniyi, B.O., et al., Extradural haematoma: a rare, but fatal complication of pyknodysostosis. Br J Neurosurg, 2008. 22(4): p. 594-5.
152. Ornetti, P., et al., Pedicle stress fracture: an unusual complication of pycnodysostosis. Clin Rheumatol, 2008. 27(3): p. 385-7.
153. Nagura, I., et al., Monteggia fracture managed by intramedullary Kirschner wire fixation with pyknodysostosis. J Orthop Sci, 2009. 14(6): p. 820-2.
154. Senel, S., et al., Mitral valve prolapse in two siblings with pyknodysostosis. Genet Couns, 2009. 20(4): p. 397-401.
155. Teissier, N., et al., Severe snoring in a child with pycnodysostosis treated with a bilateral rib graft. Cleft Palate Craniofac J, 2009. 46(1): p. 93-6.
156. Frota, R., et al., Mandibular osteomyelitis and fracture in a patient with pyknodysostosis. J Craniofac Surg, 2010. 21(3): p. 787-9.
157. Hernandez-Alfaro, F., et al., Orthognathic surgery in pycnodysostosis: a case report. Int J Oral Maxillofac Surg, 2011. 40(1): p. 110-3.
158. Yates, C.J., M.J. Bartlett, and P.R. Ebeling, An atypical subtrochanteric femoral fracture from pycnodysostosis-a lesson from nature. J Bone Miner Res, 2010. epub ahead of print.
159. Li, C.Y., et al., Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass. J Bone Miner Res, 2006. 21(6): p. 865-75.
160. Kiviranta, R., et al., Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio. Bone, 2005. 36(1): p. 159-72.
161.蔺大伟等,致密性成骨不全1例报道.中国矫形外科杂志, 2007. 15(21): p. 1674-1674.
162.杨增敏,吴莹,致密性成骨不全症1例报告.中医正骨, 2007. 19(8): p. 15-15.
163.刘军等,致密性成骨不全临床及X线诊断(附2例报告).医学影像学杂志, 2002. 12(6): p. 489-91.
164.林贞鼎,游斌,致密性成骨不全x线诊断(附1例报告).中国罕少见病杂志, 1995. 2(1): p. 46-46.
165. Cleiren, E., et al., Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet, 2001. 10(25): p. 2861-7.
166. Tsuchiya, M., et al., Comparison of expression patterns of cathepsin Kand MMP-9 in odontoclasts and osteoclasts in physiological root resorption in the rat molar. Arch Histol Cytol, 2008. 71(2): p. 89-100.
167. Yoshimatsu, M., et al., Experimental model of tooth movement by orthodontic force in mice and its application to tumor necrosis factor receptor-deficient mice. J Bone Miner Metab, 2006. 24(1): p. 20-7.
168. Varghese, B.J., et al., Bovine deciduous dentine is more susceptible to osteoclastic resorption than permanent dentine: results of quantitative analyses. J Bone Miner Metab, 2006. 24(3): p. 248-54.
169. Tsukamoto-Tanaka, H., et al., Histochemical and immunocytochemical study of hard tissue formation in dental pulp during the healing process in rat molars after tooth replantation. Cell Tissue Res, 2006. 325(2): p. 219-29.
170. Ida-Yonemochi, H., et al., Recruitment of osteoclasts in the mandible of osteopetrotic (op/op) mice. Eur J Oral Sci, 2004. 112(2): p. 148-55.
171. Okaji, M., et al., The regulation of bone resorption in tooth formation and eruption processes in mouse alveolar crest devoid of cathepsin k. J Pharmacol Sci, 2003. 91(4): p. 285-94.
172. Linsuwanont, B., et al., Localization of cathepsin K in bovine odontoclasts during deciduous tooth resorption. Calcif Tissue Int, 2002. 70(2): p. 127-33.
173. Oshiro, T., et al., Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NFkappaB ligand in odontoclasts during physiological root resorption of human deciduous teeth. Anat Rec, 2001. 264(3): p. 305-11.
174. Watanabe, J., et al., Cytochemical and ultrastructural examination of apoptotic odontoclasts induced by bisphosphonate administration. CellTissue Res, 2000. 301(3): p. 375-87.
175. Sato, Y., et al., Bisphosphonate administration alters subcellular localization of vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during experimental movement of rat molars. Anat Rec, 2000. 260(1): p. 72-80.
176. Kobayashi, Y., et al., Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J Bone Miner Res, 2000. 15(10): p. 1924-34.
177.于世凤,口腔组织病理学.第六版. 2007,北京:人民卫生出版社.
178. Kawahara, K., et al., Radiographic observations of pyknodysostosis. Report of a case. Oral Surg Oral Med Oral Pathol, 1977. 44(3): p. 476-82.
179.张立智,蒋垚,骨免疫学研究进展.国际骨科学杂志, 2009. 30(4): p. 218-20.
180. Sallusto, F. and A. Lanzavecchia, Human Th17 cells in infection and autoimmunity. Microbes and Infection, 2009. 11(5): p. 620-624.
181. Miossec, P., IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect, 2009. 11(5): p. 625-30.
182. Mesquita Jr, D., et al., Autoimmune diseases in the TH17 era. Braz J Med Biol Res, 2009. 42(6): p. 476-86.
183. Iwakura, Y., et al., The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev, 2008. 226: p. 57-79.
184. Park, S.S., S.J. Ehlenbach, and M.H. Grayson, Lung dendritic cells and IgE: the link between virus and atopy. Future Microbiol, 2008. 3(3): p. 241-5.
185.张杰,马力,慢性肺心病患者免疫功能的研究.中华内科杂志, 1993. 32(11): p. 746-9.
186. Deng, Y., et al., A comparative study on the effect of BCG-PSN and thymopeptides on T-lymphocyte subsets of normal and immunosuppressed mice. J Huazhong Univ Sci Technolog Med Sci, 2003. 23(4): p. 339-43, 347.
187. Morozov, V.G. and V.K. Khavinson, Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol, 1997. 19(9-10): p. 501-5.
188. Zhang, M. and M. Ma, Clinical application and improvement of the total glucosides of peony. Journal of Pediatric Pharmacy, 2006. 12(1): p. 48-50.
189. Wang, X., M. Chen, and S. Xu, Effects of total glueosides of paeony (TGP) on immune system. Chinese Journal of Pathophysiology 1991 7(6): p. 609-11.
190.夏爱丽等, 95例大Y染色体核型的临床效应分析.浙江临床医学, 2008. 10(4): p. 440-1.
191.何湘娇等,长沙地区大Y染色体核型98例临床效应.中国优生与遗传杂志, 2010. 18(2): p. 51-51.
192. Boyden, L.M., et al., High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med, 2002. 346(20): p. 1513-21.
193. Sobacchi, C., et al., Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet, 2007. 39(8): p. 960-2.
194. Blair, H.C., et al., In vitro differentiation of CD14 cells fromosteopetrotic subjects: contrasting phenotypes with TCIRG1, CLCN7, and attachment defects. J Bone Miner Res, 2004. 19(8): p. 1329-38.
195. Quarello, P., et al., Severe malignant osteopetrosis caused by a GL gene mutation. J Bone Miner Res, 2004. 19(7): p. 1194-9.
196. Milhaud, G., et al., Curing of the congenital osteopetrosis of "op" rats by thymus grafts. C R Acad Sci Hebd Seances Acad Sci D, 1976. 283(5): p. 531-3.
197. Zhang, Z.L., et al., Identification of the CLCN7 gene mutations in two Chinese families with autosomal dominant osteopetrosis (type II). J Bone Miner Metab, 2009. 27(4): p. 444-51.
198. Waguespack, S.G., et al., Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutation. J Clin Endocrinol Metab, 2007. 92(3): p. 771-8.
199. Johnston, C.C., Jr., et al., Osteopetrosis. A clinical, genetic, metabolic, and morphologic study of the dominantly inherited, benign form. Medicine (Baltimore), 1968. 47(2): p. 149-67.
200. Benichou, O.D., J.D. Laredo, and M.C. de Vernejoul, Type II autosomal dominant osteopetrosis (Albers-Schonberg disease): clinical and radiological manifestations in 42 patients. Bone, 2000. 26(1): p. 87-93.
201. Bollerslev, J., Osteopetrosis. A genetic and epidemiological study. Clin Genet, 1987. 31(2): p. 86-90.
202. Kruse, J.J., et al., Ossification of the ligamentum flavum as a cause of myelopathy in North America: report of three cases. J Spinal Disord, 2000. 13(1): p. 22-5.
203. Waguespack, S.G., et al., Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. J Bone Miner Res, 2003.18(8): p. 1513-8.
204. Takacs, I., et al., Bone mineral density and laboratory evaluation of a type II autosomal dominant osteopetrosis carrier. Am J Med Genet, 1999. 85(1): p. 9-12.
205. Waguespack, S.G., et al., Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but does not identify gene carriers. J Clin Endocrinol Metab, 2002. 87(5): p. 2212-7.
206. Campos-Xavier, A.B., et al., Intrafamilial phenotypic variability of osteopetrosis due to chloride channel 7 (CLCN7) mutations. Am J Med Genet A, 2005. 133A(2): p. 216-8.
207.Letizia, C., et al., Type II benign osteopetrosis (Albers-Schonberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations. Calcif Tissue Int, 2004. 74(1): p. 42-6.
208. Lam, C.W., et al., DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: standardization of molecular investigations of genetic diseases due to consanguinity. J Hum Genet, 2007. 52(1): p. 98-101.
209. Farronato, G., et al., Orthodontic treatment in a patient with cleidocranial dysostosis. Angle Orthod, 2009. 79(1): p. 178-85.
210. Lossdorfer, S., et al., The role of periodontal ligament cells in delayed tooth eruption in patients with cleidocranial dysostosis. J Orofac Orthop, 2009. 70(6): p. 495-510.
211. Manjunath, K., et al., Cementum analysis in cleidocranial dysostosis. Indian J Dent Res, 2008. 19(3): p. 253-6.
212. Vakili, R. and F. Jalali, Hypogonadotropic hypogonadism associated withcleidocranial dysostosis. J Pediatr Endocrinol Metab, 2005. 18(9): p. 917-9.
213. Marks, S.C., Jr., Osteoclast biology: lessons from mammalian mutations. Am J Med Genet, 1989. 34(1): p. 43-54.
214. Popoff, S.N. and G.B. Schneider, Animal models of osteopetrosis: the impact of recent molecular developments on novel strategies for therapeutic intervention. Mol Med Today, 1996. 2(8): p. 349-58.
215. Tiffee, J.C., et al., Dental abnormalities associated with failure of tooth eruption in src knockout and op/op mice. Calcif Tissue Int, 1999. 65(1): p. 53-8.
216. Lu, X., et al., A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots. Eur J Oral Sci, 2009. 117(6): p. 625-35.
217. Jalevik, B., A. Fasth, and G. Dahllof, Dental development after successful treatment of infantile osteopetrosis with bone marrow transplantation. Bone Marrow Transplant, 2002. 29(6): p. 537-40.
218. Hou, J., Z. Situ, and X. Duan, ClC chloride channels in tooth germ and odontoblast-like MDPC-23 cells. Arch Oral Biol, 2008. 53(9): p. 874-8.
219. Li, J.Y., et al., Temporal and spatial expression of TGF-beta2 in tooth crown development in mouse first lower molar. Eur J Histochem, 2008. 52(4): p. 243-50.
2. Noble, B., Bone microdamage and cell apoptosis. Eur Cell Mater, 2003. 6: p. 46-55.
3. Burr, D.B., Targeted and nontargeted remodeling. Bone, 2002. 30(1): p. 2-4.
4. Parfitt, A.M., Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone, 2002. 30(1): p. 5-7.
5. Takahashi, H., B. Epker, and H.M. Frost, Resorption Precedes Formative Activity. Surg Forum, 1964. 15: p. 437-8.
6. Hattner, R., B.N. Epker, and H.M. Frost, Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature, 1965. 206(983): p. 489-90.
7. Martin, T.J., Hormones in the coupling of bone resorption and formation. Osteoporos Int, 1993. 3 Suppl 1: p. 121-5.
8. Martin, T.J. and N.A. Sims, Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med, 2005. 11(2): p. 76-81.
9. Roodman, G.D., Cell biology of the osteoclast. Exp Hematol, 1999. 27(8): p. 1229-41.
10. Tatsumi, S., et al., Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab, 2007. 5(6): p. 464-75.
11. Dodds, R.A., et al., Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces: an in vitro and ex vivo study of remodeling bone. J Bone Miner Res, 1995. 10(11): p. 1666-80.
12. Everts, V., et al., The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res, 2002. 17(1): p. 77-90.
13. Mulari, M.T., et al., Osteoblast-like cells complete osteoclastic bone resorption and form new mineralized bone matrix in vitro. Calcif Tissue Int, 2004. 75(3): p. 253-61.
14. Tran Van, P., A. Vignery, and R. Baron, An electron-microscopic study of the bone-remodeling sequence in the rat. Cell Tissue Res, 1982. 225(2): p. 283-92.
15. Huffer, W.E., Morphology and biochemistry of bone remodeling: possible control by vitamin D, parathyroid hormone, and other substances. Lab Invest, 1988. 59(4): p. 418-42.
16. Martin, T.J. and E. Seeman, New mechanisms and targets in the treatment of bone fragility. Clin Sci (Lond), 2007. 112(2): p. 77-91.
17. Segovia-Silvestre, T., et al., Advances in osteoclast biology resulting from the study of osteopetrotic mutations. Hum Genet, 2009. 124(6): p. 561-77.
18. Marks, S.C., Jr. and D.G. Walker, The hematogenous origin of osteoclasts: experimental evidence from osteopetrotic (microphthalmic) mice treated with spleen cells from beige mouse donors. Am J Anat, 1981. 161(1): p. 1-10.
19. Roodman, G.D., Regulation of osteoclast differentiation. Ann N Y Acad Sci, 2006. 1068: p. 100-9.
20. Helfrich, M.H., R.H. Mieremet, and C.W. Thesingh, Osteoclast formation in vitro from progenitor cells present in the adult mouse circulation. J Bone Miner Res, 1989. 4(3): p. 325-34.
21. Thesingh, C.W., Formation sites and distribution of osteoclast progenitor cells during the ontogeny of the mouse. Dev Biol, 1986. 117(1): p. 127-34.
22. Chalhoub, N., et al., Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human. Nat Med, 2003. 9(4): p. 399-406.
23. Findlay, D.M. and T.J. Martin, Receptors of calciotropic hormones. Horm Metab Res, 1997. 29(3): p. 128-34.
24. Frattini, A., et al., Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet, 2000. 25(3): p. 343-6.
25. Gelb, B.D., et al., Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science, 1996. 273(5279): p. 1236-8.
26. Hayman, A.R., et al., Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis. Development, 1996. 122(10): p. 3151-62.
27. Kornak, U., et al., Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell, 2001. 104(2): p. 205-15.
28. Sly, W.S., et al., Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci U S A, 1983. 80(9): p. 2752-6.
29. Vu, T.H., et al., MMP-9/gelatinase B is a key regulator of growth plateangiogenesis and apoptosis of hypertrophic chondrocytes. Cell, 1998. 93(3): p. 411-22.
30. Del Fattore, A., A. Cappariello, and A. Teti, Genetics, pathogenesis and complications of osteopetrosis. Bone, 2008. 42(1): p. 19-29.
31. Boyle, W.J., W.S. Simonet, and D.L. Lacey, Osteoclast differentiation and activation. Nature, 2003. 423(6937): p. 337-42.
32. Wiktor-Jedrzejczak, W., et al., Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci U S A, 1990. 87(12): p. 4828-32.
33. Arai, F., et al., Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med, 1999. 190(12): p. 1741-54.
34. Lacey, D.L., et al., Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell, 1998. 93(2): p. 165-76.
35. Li, J., et al., RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A, 2000. 97(4): p. 1566-71.
36. Simonet, W.S., et al., Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell, 1997. 89(2): p. 309-19.
37. Yasuda, H., et al., Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology, 1998. 139(3): p. 1329-37.
38. Eghbali-Fatourechi, G., et al., Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest, 2003. 111(8): p. 1221-30.
39. Helfrich, M.H., Osteoclast diseases and dental abnormalities. Arch Oral Biol, 2005. 50(2): p. 115-22.
40. Stenbeck, G., Formation and function of the ruffled border in osteoclasts. Semin Cell Dev Biol, 2002. 13(4): p. 285-92.
41. Li, Y.P., et al., Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nat Genet, 1999. 23(4): p. 447-51.
42. Kornak, U., et al., Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Hum Mol Genet, 2000. 9(13): p. 2059-63.
43. Scimeca, J.C., et al., The gene encoding the mouse homologue of the human osteoclast-specific 116-kDa V-ATPase subunit bears a deletion in osteosclerotic (oc/oc) mutants. Bone, 2000. 26(3): p. 207-13.
44. Blair, H.C., et al., Osteoclastic bone resorption by a polarized vacuolar proton pump. Science, 1989. 245(4920): p. 855-7.
45. Blair, H.C., et al., Passive chloride permeability charge coupled to H(+)-ATPase of avian osteoclast ruffled membrane. Am J Physiol, 1991. 260(6 Pt 1): p. C1315-24.
46. Henriksen, K., et al., Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am J Pathol, 2004. 164(5): p. 1537-45.
47. Karsdal, M.A., et al., Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am J Pathol, 2005. 166(2): p. 467-76.
48. Baron, R., et al., Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization ofa 100-kD lysosomal membrane protein at the osteoclast ruffled border. J Cell Biol, 1985. 101(6): p. 2210-22.
49. Tolar, J., S.L. Teitelbaum, and P.J. Orchard, Osteopetrosis. N Engl J Med, 2004. 351(27): p. 2839-49.
50. Teti, A., et al., Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts. J Clin Invest, 1989. 83(1): p. 227-33.
51. Jansen, I.D., et al., Ae2(a,b)-deficient mice exhibit osteopetrosis of long bones but not of calvaria. FASEB J, 2009. 23(10): p. 3470-81.
52. Bossard, M.J., et al., Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem, 1996. 271(21): p. 12517-24.
53. Saftig, P., et al., Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A, 1998. 95(23): p. 13453-8.
54. Gowen, M., et al., Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res, 1999. 14(10): p. 1654-63.
55. Nishi, Y., et al., Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res, 1999. 14(11): p. 1902-8.
56. Henriksen, K., et al., Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification. J Bone Miner Res, 2006. 21(1): p. 58-66.
57. Nesbitt, S.A. and M.A. Horton, Trafficking of matrix collagens through bone-resorbing osteoclasts. Science, 1997. 276(5310): p. 266-9.
58. Salo, J., et al., Removal of osteoclast bone resorption products bytranscytosis. Science, 1997. 276(5310): p. 270-3.
59. Jentsch, T.J., CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Crit Rev Biochem Mol Biol, 2008. 43(1): p. 3-36.
60. Zhao, Q., et al., CLC-7: a potential therapeutic target for the treatment of osteoporosis and neurodegeneration. Biochem Biophys Res Commun, 2009. 384(3): p. 277-9.
61. Kida, Y., et al., Localization of mouse CLC-6 and CLC-7 mRNA and their functional complementation of yeast CLC gene mutant. Histochem Cell Biol, 2001. 115(3): p. 189-94.
62.殷丽天等,氯离子通道CIC家族的结构特点与功能研究.山西医科大学学报, 2006. 37(1): p.100-2.
63. Fukuda, M., Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem, 1991. 266(32): p. 21327-30.
64. Eskelinen, E.L., Y. Tanaka, and P. Saftig, At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol, 2003. 13(3): p. 137-45.
65. Lange, P.F., et al., ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature, 2006. 440(7081): p. 220-3.
66. Graves, A.R., et al., The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes. Nature, 2008. 453(7196): p. 788-92.
67. Kasper, D., et al., Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J, 2005. 24(5): p. 1079-91.
68. Jentsch, T.J., I. Neagoe, and O. Scheel, CLC chloride channels andtransporters. Curr Opin Neurobiol, 2005. 15(3): p. 319-25.
69. Frattini, A., et al., Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res, 2003. 18(10): p. 1740-7.
70. Berdowska, I., Cysteine proteases as disease markers. Clinica Chimica Acta, 2004. 342(1-2): p. 41-69.
71. LaLonde, J.M., et al., The crystal structure of human procathepsin K. Biochemistry, 1999. 38(3): p. 862-9.
72. Schilling, A.F., et al., High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin K. Osteoporos Int, 2007. 18(5): p. 659-69.
73. Donnarumma, M., et al., Molecular analysis and characterization of nine novel CTSK mutations in twelve patients affected by pycnodysostosis. Mutation in brief #961. Online. Hum Mutat, 2007. 28(5): p. 524.
74. Hou, W.S., et al., Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis. J Clin Invest, 1999. 103(5): p. 731-8.
75. Sivaraman, J., et al., Crystal structure of wild-type human procathepsin K. Protein Sci, 1999. 8(2): p. 283-90.
76. McQueney, M.S., et al., Autocatalytic activation of human cathepsin K. J Biol Chem, 1997. 272(21): p. 13955-60.
77. Turk, B., V. Turk, and D. Turk, Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol Chem, 1997. 378(3-4): p. 141-50.
78. Mujawar, Q., et al., Pycnodysostosis with unusual findings: a case report.Cases J, 2009. 2: p. 6544.
79. Lecaille, F., D. Bromme, and G. Lalmanach, Biochemical properties and regulation of cathepsin K activity. Biochimie, 2008. 90(2): p. 208-26.
80. Podgorski, I., Future of anticathepsin K drugs: dual therapy for skeletal disease and atherosclerosis? Future Med Chem, 2009. 1(1): p. 21-34.
81. Bromme, D. and J. Kaleta, Thiol-dependent cathepsins: pathophysiological implications and recent advances in inhibitor design. Curr Pharm Des, 2002. 8(18): p. 1639-58.
82. Chen, W., et al., Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence. Hum Mol Genet, 2007. 16(4): p. 410-23.
83. Alibhai, Z.A., et al., Presentation and management of chronic osteomyelitis in an African patient with pycnodysostosis. Oral Dis, 1999. 5(1): p. 87-9.
84. Karkabi, S., et al., Pyknodysostosis: imaging and laboratory observations. Calcif Tissue Int, 1993. 53(3): p. 170-3.
85. Gowen, M., et al., Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res, 1999. 14(10): p. 1654-63.
86. Asagiri, M., et al., Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science, 2008. 319(5863): p. 624-7.
87. Liu, J., et al., Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol, 2004. 24(8): p. 1359-66.
88. Lutgens, S.P., et al., Cathepsin cysteine proteases in cardiovascular disease. FASEB J, 2007. 21(12): p. 3029-41.
89. Balemans, W., L. Van Wesenbeeck, and W. Van Hul, A clinical andmolecular overview of the human osteopetroses. Calcif Tissue Int, 2005. 77(5): p. 263-74.
90. Vernejoul, M.-C.d., A. Schulz, and M. Uwe Kornak, PhD, CLCN7-Related Osteopetrosis. [http://www.ncbi.nlm.nih.gov/books/NBK1127/]
91. Nii, A., et al., Mild osteopetrosis in the microphthalmia-oak ridge mouse. A model for intermediate autosomal recessive osteopetrosis in humans. Am J Pathol, 1995. 147(6): p. 1871-82.
92. Campos-Xavier, A.B., et al., Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis. Hum Genet, 2003. 112(2): p. 186-9.
93. Rysavy, M., K.P. Arun, and A. Wozniak, Fracture treatment in intermediate autosomal recessive osteopetrosis. Orthopedics, 2007. 30(7): p. 577-80.
94. Selby, P.L., et al., Guidelines on the management of Paget's disease of bone. Bone, 2002. 31(3): p. 366-73.
95. Scarsbrook, A., M. Brown, and D. Wilson, UK guidelines on management of Paget's disease of bone. Rheumatology (Oxford), 2004. 43(3): p. 399-400.
96. Takata, S., et al., Guidelines for diagnosis and management of Paget's disease of bone in Japan. J Bone Miner Metab, 2006. 24(5): p. 359-67.
97. Cundy, T., et al., A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet, 2002. 11(18): p. 2119-27.
98. Nakatsuka, K., Y. Nishizawa, and S.H. Ralston, Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bpduplication in the TNFRSF11A gene. J Bone Miner Res, 2003. 18(8): p. 1381-5.
99. Whyte, M.P., et al., Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease. J Bone Miner Res, 2000. 15(12): p. 2330-44.
100.Wallace, R.G., et al., Familial expansile osteolysis. Clin Orthop Relat Res, 1989(248): p. 265-77.
101. Fleming, K.W., G. Barest, and O. Sakai, Dental and facial bone abnormalities in pyknodysostosis: CT findings. AJNR Am J Neuroradiol, 2007. 28(1): p. 132-4.
102. Naeem, M., S. Sheikh, and W. Ahmad, A mutation in CTSK gene in an autosomal recessive pycnodysostosis family of Pakistani origin. BMC Med Genet, 2009. 10: p. 76.
103. Gelb, B.D., J.G. Edelson, and R.J. Desnick, Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping. Nat Genet, 1995. 10(2): p. 235-7.
104. Gelb, B.D., et al., Cathepsin K: isolation and characterization of the murine cDNA and genomic sequence, the homologue of the human pycnodysostosis gene. Biochem Mol Med, 1996. 59(2): p. 200-6.
105. Polymeropoulos, M.H., et al., The gene for pycnodysostosis maps to human chromosome 1cen-q21. Nat Genet, 1995. 10(2): p. 238-9.
106. Rothenbuhler, A., et al., Near normalization of adult height and body proportions by growth hormone in pycnodysostosis. J Clin Endocrinol Metab, 2010. 95(6): p. 2827-31.
107. Osimani, S., et al., Craniosynostosis: A rare complication of pycnodysostosis. Eur J Med Genet, 2010. 53(2): p. 89-92.
108. Laffranchi, L., et al., Use of CBCT in the orthodontic diagnosis of apatient with pycnodysostosis. Minerva Stomatol, 2010. 59(11-12): p. 653-61.
109. Khan, B., Z. Ahmed, and W. Ahmad, A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosis. J Investig Med, 2010. 58(5): p. 720-4.
110. Bertola, D., et al., Craniosynostosis in pycnodysostosis: broadening the spectrum of the cranial flat bone abnormalities. Am J Med Genet A, 2010. 152A(10): p. 2599-603.
111. Li, H.Y., et al., Molecular analysis of a novel cathepsin K gene mutation in a Chinese child with pycnodysostosis. J Int Med Res, 2009. 37(1): p. 264-9.
112. Chavassieux, P., et al., Mechanisms of the anabolic effects of teriparatide on bone: insight from the treatment of a patient with pycnodysostosis. J Bone Miner Res, 2008. 23(7): p. 1076-83.
113. Fratzl-Zelman, N., et al., Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J Clin Endocrinol Metab, 2004. 89(4): p. 1538-47.
114. Everts, V., et al., Cathepsin K deficiency in pycnodysostosis results in accumulation of non-digested phagocytosed collagen in fibroblasts. Calcif Tissue Int, 2003. 73(4): p. 380-6.
115. Fujita, Y., et al., Novel mutations of the cathepsin K gene in patients with pycnodysostosis and their characterization. J Clin Endocrinol Metab, 2000. 85(1): p. 425-31.
116. Haagerup, A., et al., Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population. Eur J Hum Genet, 2000. 8(6): p. 431-6.
117. Ho, N., et al., Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein. J Bone Miner Res, 1999. 14(10): p. 1649-53.
118. Nishi, Y., et al., Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. J Bone Miner Res, 1999. 14(11): p. 1902-8.
119. Gelb, B.D., et al., Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis. Am J Hum Genet, 1998. 62(4): p. 848-54.
120. Johnson, M.R., et al., A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis. Genome Res, 1996. 6(11): p. 1050-5.
121. Gelb, B.D., et al., Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science, 1996. 273(5279): p. 1236-8.
122. Toral-Lopez, J., et al., Familial Pycnodysostosis: Identification of a Novel Mutation in the CTSK Gene (Cathepsin K). J Investig Med, 2011. 59(2):277-80.
123. Darcan, S., et al., A case of pycnodysostosis with growth hormone deficiency. Clin Genet, 1996. 50(5): p. 422-5.
124. Schmitz, J.P., et al., Mandibular reconstruction in a patient with pyknodysostosis. J Oral Maxillofac Surg, 1996. 54(4): p. 513-7.
125. Soliman, A.T., et al., Defective growth hormone secretion in children with pycnodysostosis and improved linear growth after growth hormone treatment. Arch Dis Child, 1996. 75(3): p. 242-4.
126. Mocan, H., et al., Pyknodysostosis: hemangioma of the skull as a new finding. Genet Couns, 1997. 8(3): p. 213-6.
127. Hunt, N.P., et al., The dental, craniofacial, and biochemical features of pyknodysostosis: a report of three new cases. J Oral Maxillofac Surg, 1998. 56(4): p. 497-504.
128. O'Connell, A.C., M.T. Brennan, and C.A. Francomano, Pycnodysostosis: orofacial manifestations in two pediatric patients. Pediatr Dent, 1998. 20(3): p. 204-7.
129. Agarwal, I., C. Kirubakaran, and G. Sridhar, Pyknodysostosis: a report of two siblings with unusual manifestations. Ann Trop Paediatr, 1999. 19(3): p. 301-5.
130. Bathi, R.J. and V.N. Masur, Pyknodysostosis--a report of two cases with a brief review of the literature. Int J Oral Maxillofac Surg, 2000. 29(6): p. 439-42.
131. Landa, S., et al., Maxillofacial alterations in a family with pycnodysostosis. Med Oral, 2000. 5(3): p. 169-176.
132. Thomas, N., et al., Association of central giant-cell granuloma of the maxilla with pyknodysostosis. Br J Oral Maxillofac Surg, 2000. 38(2): p. 159-60.
133. Kirita, T., et al., 2010-7-18 Mandibular reconstruction using a vascularised fibula osteocutaneous flap in a patient with pyknodysostosis. Br J Plast Surg, 2001. 54(8): p. 712-4.
134. Soliman, A.T., et al., Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. Metabolism, 2001. 50(8): p. 905-11.
135. Ram, P.B., S.K. Ram, and H. Neitzschman, Radiology case of the month. Sclerotic bone disease in an 8-year-old dwarf. Pycnodysostosis. J La State Med Soc, 2002. 154(6): p. 287-8.
136. Zenke, M.S., et al., Pycnodysostosis associated with spondylolysis. Arch Orthop Trauma Surg, 2002. 122(4): p. 248-50.
137. Karakurt, L., et al., Pycnodysostosis associated with bilateral congenital pseudarthrosis of the clavicle. Arch Orthop Trauma Surg, 2003. 123(2-3): p. 125-7.
138. Kundu, Z.S., et al., Subtrochanteric fracture managed by intramedullary nail in a patient with pycnodysostosis. Joint Bone Spine, 2004. 71(2): p. 154-6.
139. Norholt, S.E., J.Bjerregaard, and L. Mosekilde, Maxillary distraction osteogenesis in a patient with pycnodysostosis: a case report. J Oral Maxillofac Surg, 2004. 62(8): p. 1037-40.
140. Singh, A.R., et al., Pyknodysostosis: visceral manifestations and simian crease. Indian J Pediatr, 2004. 71(5): p. 453-5.
141. Kato, H., et al., Mandibular osteomyelitis and fracture successfully treated with vascularised iliac bone graft in a patient with pycnodysostosis. Br J Plast Surg, 2005. 58(2): p. 263-6.
142. Muto, T., et al., Pharyngeal narrowing as a common feature in pycnodysostosis--a cephalometric study. Int J Oral Maxillofac Surg, 2005. 34(6): p. 680-5.
143. Moniz, N., et al., Mandibular reconstruction with autogenous graft in patient presenting pyknodysostosis: case report. J Oral Maxillofac Surg, 2006. 64(8): p. 1292-5.
144. Wadia, F., N. Shah, and M. Porter, Bilateral charnley low-friction arthroplasty with cement in a patient with pyknodysostosis. A case report. J Bone Joint Surg Am, 2006. 88(8): p. 1846-8.
145. Dimitrakopoulos, I., C. Magopoulos, and T. Katopodi, MandibularOsteomyelitis in a Patient With Pyknodysostosis: A Case Report of a
50-Year Misdiagnosis. J Oral Maxillofac Surg 2007. 65(3): p. 580-585.
146. Fonteles, C.S., et al., Cephalometric characteristics and dentofacial abnormalities of pycnodysostosis: report of four cases from Brazil. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2007. 104(4): p. e83-90.
147. Nakase, T., et al., Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis. Arch Orthop Trauma Surg, 2007. 127(3): p. 161-5.
148. Ainola, M., et al., Erosive arthritis in a patient with pycnodysostosis: an experiment of nature. Arthritis Rheum, 2008. 58(11): p. 3394-401.
149. Alves Pereira, D., L. Berini Aytes, and C. Gay Escoda, Pycnodysostosis. A report of 3 clinical cases. Med Oral Patol Oral Cir Bucal, 2008. 13(10): p. e633-5.
150. F., S.L., et al., Pyknodysostosis: Oral ?ndings and differential diagnosis. J Indian Soc Pedod Prevent Dent 2008. Supplement: p. S23-S25.
151. Olubaniyi, B.O., et al., Extradural haematoma: a rare, but fatal complication of pyknodysostosis. Br J Neurosurg, 2008. 22(4): p. 594-5.
152. Ornetti, P., et al., Pedicle stress fracture: an unusual complication of pycnodysostosis. Clin Rheumatol, 2008. 27(3): p. 385-7.
153. Nagura, I., et al., Monteggia fracture managed by intramedullary Kirschner wire fixation with pyknodysostosis. J Orthop Sci, 2009. 14(6): p. 820-2.
154. Senel, S., et al., Mitral valve prolapse in two siblings with pyknodysostosis. Genet Couns, 2009. 20(4): p. 397-401.
155. Teissier, N., et al., Severe snoring in a child with pycnodysostosis treated with a bilateral rib graft. Cleft Palate Craniofac J, 2009. 46(1): p. 93-6.
156. Frota, R., et al., Mandibular osteomyelitis and fracture in a patient with pyknodysostosis. J Craniofac Surg, 2010. 21(3): p. 787-9.
157. Hernandez-Alfaro, F., et al., Orthognathic surgery in pycnodysostosis: a case report. Int J Oral Maxillofac Surg, 2011. 40(1): p. 110-3.
158. Yates, C.J., M.J. Bartlett, and P.R. Ebeling, An atypical subtrochanteric femoral fracture from pycnodysostosis-a lesson from nature. J Bone Miner Res, 2010. epub ahead of print.
159. Li, C.Y., et al., Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass. J Bone Miner Res, 2006. 21(6): p. 865-75.
160. Kiviranta, R., et al., Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio. Bone, 2005. 36(1): p. 159-72.
161.蔺大伟等,致密性成骨不全1例报道.中国矫形外科杂志, 2007. 15(21): p. 1674-1674.
162.杨增敏,吴莹,致密性成骨不全症1例报告.中医正骨, 2007. 19(8): p. 15-15.
163.刘军等,致密性成骨不全临床及X线诊断(附2例报告).医学影像学杂志, 2002. 12(6): p. 489-91.
164.林贞鼎,游斌,致密性成骨不全x线诊断(附1例报告).中国罕少见病杂志, 1995. 2(1): p. 46-46.
165. Cleiren, E., et al., Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet, 2001. 10(25): p. 2861-7.
166. Tsuchiya, M., et al., Comparison of expression patterns of cathepsin Kand MMP-9 in odontoclasts and osteoclasts in physiological root resorption in the rat molar. Arch Histol Cytol, 2008. 71(2): p. 89-100.
167. Yoshimatsu, M., et al., Experimental model of tooth movement by orthodontic force in mice and its application to tumor necrosis factor receptor-deficient mice. J Bone Miner Metab, 2006. 24(1): p. 20-7.
168. Varghese, B.J., et al., Bovine deciduous dentine is more susceptible to osteoclastic resorption than permanent dentine: results of quantitative analyses. J Bone Miner Metab, 2006. 24(3): p. 248-54.
169. Tsukamoto-Tanaka, H., et al., Histochemical and immunocytochemical study of hard tissue formation in dental pulp during the healing process in rat molars after tooth replantation. Cell Tissue Res, 2006. 325(2): p. 219-29.
170. Ida-Yonemochi, H., et al., Recruitment of osteoclasts in the mandible of osteopetrotic (op/op) mice. Eur J Oral Sci, 2004. 112(2): p. 148-55.
171. Okaji, M., et al., The regulation of bone resorption in tooth formation and eruption processes in mouse alveolar crest devoid of cathepsin k. J Pharmacol Sci, 2003. 91(4): p. 285-94.
172. Linsuwanont, B., et al., Localization of cathepsin K in bovine odontoclasts during deciduous tooth resorption. Calcif Tissue Int, 2002. 70(2): p. 127-33.
173. Oshiro, T., et al., Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NFkappaB ligand in odontoclasts during physiological root resorption of human deciduous teeth. Anat Rec, 2001. 264(3): p. 305-11.
174. Watanabe, J., et al., Cytochemical and ultrastructural examination of apoptotic odontoclasts induced by bisphosphonate administration. CellTissue Res, 2000. 301(3): p. 375-87.
175. Sato, Y., et al., Bisphosphonate administration alters subcellular localization of vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during experimental movement of rat molars. Anat Rec, 2000. 260(1): p. 72-80.
176. Kobayashi, Y., et al., Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J Bone Miner Res, 2000. 15(10): p. 1924-34.
177.于世凤,口腔组织病理学.第六版. 2007,北京:人民卫生出版社.
178. Kawahara, K., et al., Radiographic observations of pyknodysostosis. Report of a case. Oral Surg Oral Med Oral Pathol, 1977. 44(3): p. 476-82.
179.张立智,蒋垚,骨免疫学研究进展.国际骨科学杂志, 2009. 30(4): p. 218-20.
180. Sallusto, F. and A. Lanzavecchia, Human Th17 cells in infection and autoimmunity. Microbes and Infection, 2009. 11(5): p. 620-624.
181. Miossec, P., IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect, 2009. 11(5): p. 625-30.
182. Mesquita Jr, D., et al., Autoimmune diseases in the TH17 era. Braz J Med Biol Res, 2009. 42(6): p. 476-86.
183. Iwakura, Y., et al., The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev, 2008. 226: p. 57-79.
184. Park, S.S., S.J. Ehlenbach, and M.H. Grayson, Lung dendritic cells and IgE: the link between virus and atopy. Future Microbiol, 2008. 3(3): p. 241-5.
185.张杰,马力,慢性肺心病患者免疫功能的研究.中华内科杂志, 1993. 32(11): p. 746-9.
186. Deng, Y., et al., A comparative study on the effect of BCG-PSN and thymopeptides on T-lymphocyte subsets of normal and immunosuppressed mice. J Huazhong Univ Sci Technolog Med Sci, 2003. 23(4): p. 339-43, 347.
187. Morozov, V.G. and V.K. Khavinson, Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol, 1997. 19(9-10): p. 501-5.
188. Zhang, M. and M. Ma, Clinical application and improvement of the total glucosides of peony. Journal of Pediatric Pharmacy, 2006. 12(1): p. 48-50.
189. Wang, X., M. Chen, and S. Xu, Effects of total glueosides of paeony (TGP) on immune system. Chinese Journal of Pathophysiology 1991 7(6): p. 609-11.
190.夏爱丽等, 95例大Y染色体核型的临床效应分析.浙江临床医学, 2008. 10(4): p. 440-1.
191.何湘娇等,长沙地区大Y染色体核型98例临床效应.中国优生与遗传杂志, 2010. 18(2): p. 51-51.
192. Boyden, L.M., et al., High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med, 2002. 346(20): p. 1513-21.
193. Sobacchi, C., et al., Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet, 2007. 39(8): p. 960-2.
194. Blair, H.C., et al., In vitro differentiation of CD14 cells fromosteopetrotic subjects: contrasting phenotypes with TCIRG1, CLCN7, and attachment defects. J Bone Miner Res, 2004. 19(8): p. 1329-38.
195. Quarello, P., et al., Severe malignant osteopetrosis caused by a GL gene mutation. J Bone Miner Res, 2004. 19(7): p. 1194-9.
196. Milhaud, G., et al., Curing of the congenital osteopetrosis of "op" rats by thymus grafts. C R Acad Sci Hebd Seances Acad Sci D, 1976. 283(5): p. 531-3.
197. Zhang, Z.L., et al., Identification of the CLCN7 gene mutations in two Chinese families with autosomal dominant osteopetrosis (type II). J Bone Miner Metab, 2009. 27(4): p. 444-51.
198. Waguespack, S.G., et al., Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutation. J Clin Endocrinol Metab, 2007. 92(3): p. 771-8.
199. Johnston, C.C., Jr., et al., Osteopetrosis. A clinical, genetic, metabolic, and morphologic study of the dominantly inherited, benign form. Medicine (Baltimore), 1968. 47(2): p. 149-67.
200. Benichou, O.D., J.D. Laredo, and M.C. de Vernejoul, Type II autosomal dominant osteopetrosis (Albers-Schonberg disease): clinical and radiological manifestations in 42 patients. Bone, 2000. 26(1): p. 87-93.
201. Bollerslev, J., Osteopetrosis. A genetic and epidemiological study. Clin Genet, 1987. 31(2): p. 86-90.
202. Kruse, J.J., et al., Ossification of the ligamentum flavum as a cause of myelopathy in North America: report of three cases. J Spinal Disord, 2000. 13(1): p. 22-5.
203. Waguespack, S.G., et al., Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. J Bone Miner Res, 2003.18(8): p. 1513-8.
204. Takacs, I., et al., Bone mineral density and laboratory evaluation of a type II autosomal dominant osteopetrosis carrier. Am J Med Genet, 1999. 85(1): p. 9-12.
205. Waguespack, S.G., et al., Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but does not identify gene carriers. J Clin Endocrinol Metab, 2002. 87(5): p. 2212-7.
206. Campos-Xavier, A.B., et al., Intrafamilial phenotypic variability of osteopetrosis due to chloride channel 7 (CLCN7) mutations. Am J Med Genet A, 2005. 133A(2): p. 216-8.
207.Letizia, C., et al., Type II benign osteopetrosis (Albers-Schonberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations. Calcif Tissue Int, 2004. 74(1): p. 42-6.
208. Lam, C.W., et al., DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: standardization of molecular investigations of genetic diseases due to consanguinity. J Hum Genet, 2007. 52(1): p. 98-101.
209. Farronato, G., et al., Orthodontic treatment in a patient with cleidocranial dysostosis. Angle Orthod, 2009. 79(1): p. 178-85.
210. Lossdorfer, S., et al., The role of periodontal ligament cells in delayed tooth eruption in patients with cleidocranial dysostosis. J Orofac Orthop, 2009. 70(6): p. 495-510.
211. Manjunath, K., et al., Cementum analysis in cleidocranial dysostosis. Indian J Dent Res, 2008. 19(3): p. 253-6.
212. Vakili, R. and F. Jalali, Hypogonadotropic hypogonadism associated withcleidocranial dysostosis. J Pediatr Endocrinol Metab, 2005. 18(9): p. 917-9.
213. Marks, S.C., Jr., Osteoclast biology: lessons from mammalian mutations. Am J Med Genet, 1989. 34(1): p. 43-54.
214. Popoff, S.N. and G.B. Schneider, Animal models of osteopetrosis: the impact of recent molecular developments on novel strategies for therapeutic intervention. Mol Med Today, 1996. 2(8): p. 349-58.
215. Tiffee, J.C., et al., Dental abnormalities associated with failure of tooth eruption in src knockout and op/op mice. Calcif Tissue Int, 1999. 65(1): p. 53-8.
216. Lu, X., et al., A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots. Eur J Oral Sci, 2009. 117(6): p. 625-35.
217. Jalevik, B., A. Fasth, and G. Dahllof, Dental development after successful treatment of infantile osteopetrosis with bone marrow transplantation. Bone Marrow Transplant, 2002. 29(6): p. 537-40.
218. Hou, J., Z. Situ, and X. Duan, ClC chloride channels in tooth germ and odontoblast-like MDPC-23 cells. Arch Oral Biol, 2008. 53(9): p. 874-8.
219. Li, J.Y., et al., Temporal and spatial expression of TGF-beta2 in tooth crown development in mouse first lower molar. Eur J Histochem, 2008. 52(4): p. 243-50.