The cleavage of N-cadherin is essential for chondrocyte differentiation
The cleavage of N-cadherin is essential for chondrocyte differentiation
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DOI：
10.1016/j.bbrc.2010.08.070
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Sudo, Akihiro
中科院分区：
文献类型：
--
作者：
Nakazora, Shigeto;Matsumine, Akihiko;Sudo, Akihiro
软骨前体间充质细胞聚集成前软骨凝结是软骨形成中最早的事件之一。N-钙粘蛋白是参与软骨形成分化的关键细胞粘附分子。近年来，研究发现，ADAM 10介导的N-钙粘蛋白切割在细胞粘附、迁移、发育和信号转导中发挥重要作用。然而，N-钙粘蛋白裂解在软骨细胞分化中的意义尚未确定。在本研究中，我们发现N-钙粘蛋白的蛋白更新在ATDC 5细胞软骨形成分化的早期阶段加速。因此，我们产生了过表达野生型N-钙粘蛋白的ATDC 5细胞的亚克隆和过表达切割缺陷型N-钙粘蛋白突变体的两种类型的亚克隆，并检查这些细胞对胰岛素刺激的反应。ATDC 5细胞过度表达切割缺陷突变体严重阻碍了软骨聚集体的形成、蛋白聚糖的产生和软骨细胞标志物基因表达的诱导，如II型胶原、聚集蛋白聚糖和X型胶原。这些结果表明，N-钙粘蛋白的切割是软骨细胞分化所必需的。(C)2010年爱思唯尔公司All rights reserved.
The aggregation of chondroprogenitor mesenchymal cells into precartilage condensation represents one of the earliest events in chondrogenesis. N-cadherin is a key cell adhesion molecule implicated in chondrogenic differentiation. Recently, ADAM10-mediated cleavage of N-cadherin has been reported to play an important role in cell adhesion, migration, development and signaling. However, the significance of N-cadherin cleavage in chondrocyte differentiation has not been determined. In the present study, we found that the protein turnover of N-cadherin is accelerated during the early phase of chondrogenic differentiation in ATDC5 cells. Therefore, we generated the subclones of ATDC5 cells overexpressing wild-type N-cadherin, and two types of subclones overexpressing a cleavage-defective N-cadherin mutant, and examined the response of these cells to insulin stimulation. The ATDC5 cells overexpressing cleavage-defective mutants severely prevented the formation of cartilage aggregates, proteoglycan production and the induction of chondrocyte marker gene expression, such as type II collagen, aggrecan and type X collagen. These results suggested that the cleavage of N-cadherin is essential for chondrocyte differentiation. (C) 2010 Elsevier Inc. All rights reserved.