Matrilin-3 activates the expression of osteoarthritis-associated genes in primary human chondrocytes
Matrilin-3 activates the expression of osteoarthritis-associated genes in primary human chondrocytes
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DOI：
10.1016/j.febslet.2009.10.035
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发表时间：
2009-11-19
期刊：
影响因子：
3.5
通讯作者：
Wielckens, Klaus
中科院分区：
文献类型：
--
作者：
Klatt, Andreas R.;Klinger, Gabriele;Wielckens, Klaus
在这里，我们测试了Matrlin-3对原代人类软骨细胞骨关节炎相关基因的诱导作用。Matrlin刺激可诱导MMP1、MMP3、MMP13、COX-2、iNOS、IL-1β、TNFα、IL-6和IL-8的产生。此外，我们还展示了ADAMTS4和ADAMTS5参与了Matrlin-3的体外降解。我们提供了依赖于matrlin-3的基质降解的前馈机制的证据，在该机制中，蛋白水解性释放的matrlin-3通过IL-1β间接地诱导促炎细胞因子以及ADAMTS4和-5。ADAMTS4和ADAMTS5反过来又裂解matrlin-3，并可能从基质中释放更多matrlin-3，这可能导致软骨中进一步释放促炎细胞因子和蛋白酶。(C)2009年欧洲生化学会联合会。爱思唯尔出版公司版权所有。
Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated genes in primary human chondrocytes. Matrilin stimulation leads to the induction of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1 beta, TNF alpha, IL-6 and IL-8. Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed-forward mechanism of matrix degradation, whereby proteolytically-released matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5 indirectly via IL-1 beta. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may release more matrilin-3 from the matrix, which could lead to further release of pro-inflammatory cytokines and proteases in cartilage. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.