Cathepsins B, K, and L are regulated by a defined collagen type II peptide via activation of classical protein kinase C and p38 MAP kinase in articular chondrocytes
Cathepsins B, K, and L are regulated by a defined collagen type II peptide via activation of classical protein kinase C and p38 MAP kinase in articular chondrocytes
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DOI：
10.1074/jbc.m704915200
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发表时间：
2008-01-11
影响因子：
4.8
通讯作者：
Wiederanders, Bernd
中科院分区：
文献类型：
--
作者：
Ruettger, Anke;Schueler, Susann;Wiederanders, Bernd
细胞外基质(ECM)降解是骨关节炎(OA)的一个显著特征，其主要原因是软骨细胞的合成代谢和分解代谢过程失衡，导致软骨和骨的破坏。多种酶协同作用降解基质成分，如II型胶原、MMPs、ADAMTS和组织蛋白。蛋白水解酶产生的胶原蛋白碎片可能会促进这种破坏过程。然而，与胶原片段对软骨细胞作用相关的信号通路还没有明确的定义。目前的数据表明，II型胶原的N端肽在基因、蛋白和活性水平上促进了关节软骨细胞组织蛋白酶B、K和L的表达，至少部分是通过细胞外钙介导的。我们还证明了这种诱导与蛋白激酶C和p38MAP激酶的激活有关。
Degradation of the extracellular matrix (ECM) is a prominent feature in osteoarthritis (OA), which is mainly because of the imbalance between anabolic and catabolic processes in chondrocytes resulting in cartilage and bone destruction. Various proteases act in concert to degrade matrix components, e. g. type II collagen, MMPs, ADAMTS, and cathepsins. Protease-generated collagen fragments may foster the destructive process. However, the signaling pathways associated with the action of collagen fragments on chondrocytes have not been clearly defined. The present data demonstrate that the N-terminal telopeptide of collagen type II enhances expression of cathepsins B, K, and L in articular chondrocytes at mRNA, protein, and activity levels, mediated at least in part through extracellular calcium. We also demonstrate that the induction is associated with the activation of protein kinase C and p38 MAP kinase.