Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation - Implications for cartilage degradation in arthritis
Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation - Implications for cartilage degradation in arthritis
复制标题
DOI：
10.1002/art.22167
复制
发表时间：
2006-10-01
影响因子：
--
通讯作者：
Rowan, A. D.
中科院分区：
文献类型：
--
作者：
Barksby, H. E.;Milner, J. M.;Rowan, A. D.
Objective.我们以前曾报道了上调基质金属蛋白酶10（MMP-10）后处理的前代谢刺激的白细胞介素-1（IL-1）和制瘤素M（OSM）在软骨细胞。虽然MMP-10与MMP-3密切相关，但关于MMP-10在软骨软骨炎中的作用知之甚少。本研究的目的是确定MMP-10是否在结缔组织细胞中表达，并评估其如何促进软骨胶原溶解。MMP基因表达通过实时聚合酶链反应使用来自人关节软骨细胞和滑膜成纤维细胞的RNA进行评估，所述人关节软骨细胞和滑膜成纤维细胞用IL-1加OSM或肿瘤坏死因子α（TNF α）加OSM刺激。用特异性免疫测定法测定关节液中MMP-10的水平。在活化研究中使用重组前胶原酶。免疫组化检测MMP-10在病变关节组织中的表达。在用IL-1加OSM或TNF α加OSM刺激后，在软骨细胞和滑膜成纤维细胞中证实了MMP-10表达，并且在患有各种关节病的患者的滑液样品中检测到MMP-10。外源性MMP-10显著增强IL-1加OSM刺激的软骨的胶原溶解，MMP-10激活proMMP-1、proMMP-8和proMMP-13。免疫组化显示MMP-10存在于IL-1加OSM诱导的关节炎模型的滑膜和软骨中以及患病的人类组织样品中。我们证实，滑膜成纤维细胞和关节软骨细胞表达MMP-10后处理与促代谢刺激。此外，滑液MMP-10的可检测水平和病变关节组织中这种蛋白酶的组织学检测强烈暗示MMP-10在关节炎期间的软骨降解中。MMP-10超活化与软骨降解相关的胶原原酶的能力表明，这种活化代表了MMP促进关节炎组织破坏的重要机制。
Objective. We have previously reported the up-regulation of matrix metalloproteinase 10 (MMP-10) following treatment with the procatabolic stimulus of interleukin-1 (IL-1) and oncostatin M (OSM) in chondrocytes. Although MMP-10 is closely related to MMP-3, little is known about the role of MMP-10 in cartilage catabolism. The purpose of this study was to determine whether MMP-10 is expressed in connective tissue cells and to assess how it may contribute to cartilage collagenolysis.Methods. MMP gene expression was assessed by real-time polymerase chain reaction using RNA from human articular chondrocytes and synovial fibroblasts stimulated with IL-1 plus OSM or tumor necrosis factor a (TNF alpha) plus OSM. Synovial fluid levels of MMP-10 were determined by specific immunoassay. Recombinant procollagenases were used in activation studies. Immunohistochemistry assessed MMP-10 expression in diseased joint tissues.Results. MMP-10 expression was confirmed in both chondrocytes and synovial fibroblasts following stimulation with either IL-1 plus OSM or TNF alpha plus OSM, and MMP-10 was detected in synovial fluid samples from patients with various arthropathies. Exogenous MMP-10 significantly enhanced collagenolysis from IL-1 plus OSM-stimulated cartilage, and MMP-10 activated proMMP-1, proMMP-8, and proMMP-13. Immunohistochemistry revealed the presence of MMP-10 in the synovium and cartilage of an IL-1 plus OSM-induced model of arthritis as well as in samples of diseased human tissues.Conclusion. We confirm that both synovial fibroblasts and articular chondrocytes express MMP-10 following treatment with procatabolic stimuli. Furthermore, the detectable levels of synovial fluid MMP-10 and the histologic detection of this proteinase in diseased joint tissues strongly implicate MMP-10 in the cartilage degradome during arthritis. The ability of MMP-10 to superactivate procollagenases that are relevant to cartilage degradation suggests that this activation represents an important mechanism by which this MMP contributes to tissue destruction in arthritis.