WISP3–IGF1 interaction regulates chondrocyte hypertrophy
WISP3–IGF1 interaction regulates chondrocyte hypertrophy
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DOI：
10.1242/jcs.119859
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发表时间：
2013-04
影响因子：
4
通讯作者：
S. Repudi;M. Patra;M. Sen
中科院分区：
文献类型：
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作者：
S. Repudi;M. Patra;M. Sen
WISP3(Wnt Induced Secure Protein 3)是一种间充质来源的多结构域蛋白。WISP3多个结构域的突变导致进行性假性类风湿性发育不良(PPRD)，与软骨丢失和骨骼发育受限有关。尽管一些研究集中在WISP3的功能特征上，但PPRD过程中潜在的分子细节仍未解决。我们有兴趣分析WISP3在软骨完整性方面的功能。目前的研究表明，WISP3与胰岛素样生长因子1(IGF1)结合，并抑制IGF1的分泌。此外，WISP3还可抑制IGF1介导的X型胶原蛋白的表达、活性氧(ROS)的积累和碱性磷酸酶的活性，所有这些都与诱导软骨细胞肥大有关。有趣的是，IGF1和ROS反过来都会触发WISP3表达的增加。综上所述，我们的结果表明WISP3-IGF1调控环的运作，WISP3通过限制IGF1介导的软骨细胞肥大变化来保护软骨完整性，至少部分地限制了IGF1与IGF1的相互作用。
Summary WISP3 (Wnt induced secreted protein 3) is a multi-domain protein of mesenchymal origin. Mutations in several domains of WISP3 cause PPRD (progressive pseudo rheumatoid dysplasia), which is associated with cartilage loss and restricted skeletal development. Despite several studies focusing on the functional characterization of WISP3, the molecular details underlying the course of PPRD remain unresolved. We are interested in analyzing the function of WISP3 in the context of cartilage integrity. The current study demonstrates that WISP3 binds to insulin-like growth factor 1 (IGF1) and inhibits IGF1 secretion. Additionally, WISP3 curbs IGF1-mediated collagen X expression, accumulation of reactive oxygen species (ROS) and alkaline phosphatase activity, all of which are associated with the induction of chondrocyte hypertrophy. Interestingly, both IGF1 and ROS in turn trigger an increase in WISP3 expression. Together, our results are indicative of an operational WISP3–IGF1 regulatory loop whereby WISP3 preserves cartilage integrity by restricting IGF1-mediated hypertrophic changes in chondrocytes, at least partly, upon interaction with IGF1.