Genetic mouse models for the functional analysis of the perifibrillar components collagen IX, COMP and matrilin-3: Implications for growth cartilage differentiation and endochondral ossification.
Genetic mouse models for the functional analysis of the perifibrillar components collagen IX, COMP and matrilin-3: Implications for growth cartilage differentiation and endochondral ossification.
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用于原纤维周围成分胶原蛋白 IX、COMP 和 matrilin-3 功能分析的遗传小鼠模型：对生长软骨分化和软骨内骨化的影响。
DOI：
10.14670/hh-24.1067
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发表时间：
2009
影响因子：
2
通讯作者：
S. Grässel
中科院分区：
文献类型：
--
作者：
F. Zaucke;S. Grässel
两个超分子室、原纤维和原纤维外基质的相互作用是软骨细胞外基质稳定性和完整性的先决条件。纤维外周由 IX 胶原、基质蛋白和软骨寡聚基质蛋白 (COMP) 等成分组成，构成介导两个区室之间相互作用的界面。这些外周大分子的突变会导致广泛的骨骼疾病，例如假性软骨发育不全（PSACH）和多发性骨骺发育不良（MED），严重影响人类软骨生长基质的组织和完整性。胶原蛋白 IX、matrilin-3 和 COMP 及其组合的转基因和敲除小鼠模型显示出不同严重程度的软骨异常和病理。缺乏 IX 胶原蛋白似乎会导致最严重的生长板表型，其形态组织受到严重干扰，影响长骨的大小和形状。值得注意的是，在缺乏其他大分子或携带突变的转基因小鼠中观察到类似的生长板表型，包括蛋白多糖含量不规则、细胞中心区域减少、具有非典型形状和定向软骨细胞的紊乱增殖柱以及肥大区的改变。这些包括胶原蛋白 II 和 XI、整合素亚基、整合素连接激酶 (ILK)、HIF-1α、VEGFα 和肿瘤抑制因子 PTEN。值得注意的是，诸如 Kif3alpha、polaris 或 Smo/Gli 等纤毛蛋白的突变严重影响软骨细胞移动和排列成柱的能力。各种不同的、不相关的软骨大分子的缺失或突变变化显然会导致生长软骨的类似病理和异常，这表明潜在的分子机制数量有限。
The mutual interaction of the two supramolecular compartments, the fibrillar and extrafibrillar matrix is a prerequisite for stability and integrity of the cartilage extracellular matrix. The fibrillar periphery, composed of collagen IX, matrilins and cartilage oligomeric matrix protein (COMP) among other components, constitutes the interface which mediates interactions between the two compartments. Mutations in these peripheral macromolecules cause a broad spectrum of skeletal conditions such as pseudo-achondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which severely affect the organization and integrity of the cartilage growth matrix in humans. Transgenic and knockout mouse models for collagen IX, matrilin-3 and COMP and combinations thereof display cartilage abnormalities and pathologies of varying severity. Absence of collagen IX appears to cause the most severe growth plate phenotype with a profoundly disturbed morphological organization affecting size and shape of the long bones. Notably, similar growth plate phenotypes, including irregularities in the proteoglycan content, hypocellular central regions, disorganized proliferation columns with atypically shaped and oriented chondrocytes and alterations in the hypertrophic zone are observed in transgenic mice lacking other macromolecules or carrying mutations therein. These include collagens II and XI, integrin subunits, integrin linked kinase (ILK), HIF-1alpha, VEGFalpha and the tumor suppressor PTEN. Notably, mutations in ciliar proteins such as Kif3alpha, polaris or Smo/Gli severely affect the ability of chondrocytes to move and to become arranged in columns. Absence or mutational changes of a variety of different, non-related cartilage macromolecules apparently cause similar pathologies and abnormalities of the growth cartilage, suggesting a limited number of underlying molecular mechanisms.
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影响因子：
10.5
作者：
E. Schipani;H. Ryan;Susanna Didrickson;Tatsuya Kobayashi;M. Knight;R. Johnson
通讯作者：
E. Schipani;H. Ryan;Susanna Didrickson;Tatsuya Kobayashi;M. Knight;R. Johnson
DOI：
10.1073/pnas.88.21.9648
发表时间：
1991-11-01
影响因子：
11.1
作者：
GAROFALO, S;VUORIO, E;DECROMBRUGGHE, B
通讯作者：
DECROMBRUGGHE, B
影响因子：
6
作者：
van der Weyden, Louise;Wei, Lei;Chen, Qian
通讯作者：
Chen, Qian
影响因子：
7.5
作者：
Sun, Changbin;Wang, Lei;Zhang, Xi
通讯作者：
Zhang, Xi
影响因子：
6.9
作者：
McGlashan, S. R.;Haycraft, C. J.;Poole, C. A.
通讯作者：
Poole, C. A.