Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737orpk mice lacking the primary cilia protein polaris
Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737orpk mice lacking the primary cilia protein polaris
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DOI：
10.1016/j.matbio.2006.12.003
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发表时间：
2007-05-01
期刊：
影响因子：
6.9
通讯作者：
Poole, C. A.
中科院分区：
文献类型：
--
作者：
McGlashan, S. R.;Haycraft, C. J.;Poole, C. A.
初级纤毛是几乎所有真核细胞上发现的高度保守的细胞器。Tg 737（orpk）（orpk）小鼠在Tg 737基因中携带亚型突变，导致polaris（纤毛发生所必需的蛋白质）的缺失。Orpk小鼠有一系列的骨骼图案缺陷，并显示出生后生长发育迟缓，这表明在并置和内软骨发育缺陷。本研究采用组织形态计量学和免疫组化分析研究orpk胫骨长骨生长和软骨细胞初级纤毛表达之间的关系。整个发育中的骨骺和生长板的野生型软骨细胞表达初级纤毛，其在前7-10个细胞层中显示出远离关节面的特定取向。在orpk小鼠中，初级纤毛在极少数细胞上被识别，并且显着较短。Orpk软骨细胞也表现出细胞质微管蛋白的显著增加，这可能是纤毛组装失败的结果。orpk小鼠的生长板在长度和宽度上明显较小，在假定的关节软骨、增殖区和肥大区的细胞组织中有明显的变化。关节面和肥大区的细胞密度发生显着改变，表明附着生长和软骨内生长均存在缺陷。此外，orpk肥大的软骨细胞显示重组的F-肌动蛋白网络成应力纤维，并未能充分进行肥大，而有一个显着减少X型胶原螯合。这些数据表明，未能形成功能性初级纤毛会影响软骨细胞分化，并导致orpk生长板内的软骨细胞肥大延迟。(C)2007年Elsevier B. V./国际矩阵生物学学会。All rights reserved.
Primary cilia are highly conserved organelles found on almost all eukaryotic cells. Tg737(orpk) (orpk) mice carry a hypomorphic mutation in the Tg737 gene resulting in the loss of polaris, a protein essential for ciliogenesis. Orpk mice have an array of skeletal patterning defects and show stunted growth after birth, suggesting defects in appositional and endochondral development. This study investigated the association between orpk tibial long bone growth and chondrocyte primary cilia expression using histomorphometric and immunohistochemical analysis. Wild-type chondrocytes throughout the developing epiphysis and growth plate expressed primary cilia, which showed a specific orientation away from the articular surface in the first 7-10 cell layers. In orpk mice, primary cilia were identified on very few cells and were significantly shorter. Orpk chondrocytes also showed significant increases in cytoplasmic tubulin, a likely result of failed ciliary assembly. The growth plates of orpk mice were significantly smaller in length and width, with marked changes in cellular organization in the presumptive articular cartilage, proliferative and hypertrophic zones. Cell density at the articular surface and in the hypertrophic zone was significantly altered, suggesting defects in both appositional and endochondral growth. In addition, orpk hypertrophic chondrocytes showed re-organization of the F-actin network into stress fibres and failed to fully undergo hypertrophy, while there was a marked reduction in type X collagen sequestration. These data suggest that failure to form a functional primary cilium affects chondrocyte differentiation and results in delayed chondrocyte hypertrophy within the orpk growth plate. (C) 2007 Elsevier B.V./International Society of Matrix Biology. All rights reserved.