Binding characteristics of the osteoarthritis-associated protein asporin
Binding characteristics of the osteoarthritis-associated protein asporin
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DOI：
10.1007/s00774-009-0145-8
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发表时间：
2010-07-01
影响因子：
3.3
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Kou, Ikuyo;Nakajima, Masahiro;Ikegawa, Shiro
Asporin是一种细胞外基质(ECM)蛋白，通过调节转化生长因子-β(TGF-β)信号通路调节软骨基质基因的表达和软骨的形成。我们以前的研究表明，asporin直接与转化生长因子-β1结合，并抑制转化生长因子-β1介导的软骨基质基因的表达。然而，目前尚不清楚asporin如何与转化生长因子-β1相互作用并影响其活性。通过竞争分析，我们确定Asporin的159-205位氨基酸介导了其与转化生长因子β1的相互作用，并有效地抑制了转化生长因子β1诱导的软骨基质基因的表达。Asporin在体外也具有与II型胶原结合的能力，但其结合模式与转化生长因子-β1不同。与以往的体内研究结果不同，Asporin在体外单独或在II型胶原存在的情况下不影响转化生长因子-β1与转化生长因子-β2型受体(TβRII)的相互作用。然而，在肝素/硫酸肝素存在的情况下，阿司匹林在体外抑制了转化生长因子-β和T-βRII之间的相互作用。这些发现表明，asporin是一种重要的软骨基质蛋白，它与ECM和转化生长因子-β1结合，从而调节转化生长因子-β与其信号受体之间的相互作用。
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-beta 1 directly and inhibits TGF-beta 1-mediated expression of cartilage matrix genes. However, it is still unknown how asporin interacts with TGF-beta 1 and influences its activity. Using competition assays, we determined that amino acids 159-205 of asporin mediate its interaction with TGF-beta 1 and effectively repress TGF-beta 1-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-beta 1. In contrast with previous in vivo findings, asporin did not affect the interaction between TGF-beta 1 and the TGF-beta type II receptor (T beta RII) 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 T beta RII in vitro. These findings suggest that asporin is one of the important cartilage matrix proteins that binds to the ECM and TGF-beta 1 and thereby modulates interactions between TGF-beta and its signaling receptors.