Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Bone Miner Metab. 2010 Jul;28(4):395-402. doi: 10.1007/s00774-009-0145-8. Epub 2010 Jan 7.
Asporin is an extracellular matrix (ECM) protein that regulates cartilage matrix gene expression and cartilage formation by modulating the transforming growth factor-beta (TGF-beta) signaling pathway. Our previous studies have indicated that asporin binds to TGF-beta1 directly and inhibits TGF-beta1-mediated expression of cartilage matrix genes. However, it is still unknown how asporin interacts with TGF-beta1 and influences its activity. Using competition assays, we determined that amino acids 159-205 of asporin mediate its interaction with TGF-beta1 and effectively repress TGF-beta1-induced cartilage matrix gene expression. Asporin also has a binding ability to type II collagen in vitro, but its binding pattern is different from that of TGF-beta1. In contrast with previous in vivo findings, asporin did not affect the interaction between TGF-beta1 and the TGF-beta type II receptor (TbetaRII) by itself or in the presence of type II collagen in vitro. However, in the presence of heparin/heparan sulfate, asporin inhibits the interaction between TGF-beta and TbetaRII in vitro. These findings suggest that asporin is one of the important cartilage matrix proteins that binds to the ECM and TGF-beta1 and thereby modulates interactions between TGF-beta and its signaling receptors.
聚集蛋白是一种细胞外基质（ECM）蛋白，通过调节转化生长因子-β（TGF-β）信号通路来调节软骨基质基因表达和软骨形成。我们之前的研究表明，聚集蛋白直接与 TGF-β1 结合，并抑制 TGF-β1 介导的软骨基质基因表达。然而，聚集蛋白如何与 TGF-β1 相互作用并影响其活性仍不清楚。通过竞争实验，我们确定聚集蛋白的 159-205 个氨基酸介导其与 TGF-β1 的相互作用，并有效抑制 TGF-β1 诱导的软骨基质基因表达。聚集蛋白在体外也具有与 II 型胶原结合的能力，但结合模式与 TGF-β1 不同。与之前的体内发现相反，聚集蛋白本身或在 II 型胶原存在的情况下，并不影响 TGF-β1 与 TGF-β 型 II 受体（TbetaRII）之间的相互作用。然而，在肝素/硫酸乙酰肝素存在的情况下，聚集蛋白抑制 TGF-β 与 TbetaRII 之间的体外相互作用。这些发现表明，聚集蛋白是与细胞外基质和 TGF-β1 结合的重要软骨基质蛋白之一，从而调节 TGF-β 与其信号受体之间的相互作用。
