Barksby H E, Milner J M, Patterson A M, Peake N J, Hui W, Robson T, Lakey R, Middleton J, Cawston T E, Richards C D, Rowan A D
School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, UK.
Arthritis Rheum. 2006 Oct;54(10):3244-53. doi: 10.1002/art.22167.
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.
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 alpha (TNFalpha) 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.
MMP-10 expression was confirmed in both chondrocytes and synovial fibroblasts following stimulation with either IL-1 plus OSM or TNFalpha 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.
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.
我们之前曾报道，在软骨细胞中，用白细胞介素-1（IL-1）和抑瘤素M（OSM）的促分解代谢刺激处理后，基质金属蛋白酶10（MMP-10）会上调。尽管MMP-10与MMP-3密切相关，但关于MMP-10在软骨分解代谢中的作用知之甚少。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。
使用来自经IL-1加OSM或肿瘤坏死因子α（TNFα）加OSM刺激的人关节软骨细胞和滑膜成纤维细胞的RNA，通过实时聚合酶链反应评估MMP基因表达。通过特异性免疫测定法测定滑膜液中MMP-10的水平。在激活研究中使用重组原胶原酶。免疫组织化学评估患病关节组织中MMP-10的表达。
在用IL-1加OSM或TNFα加OSM刺激后，软骨细胞和滑膜成纤维细胞中均证实有MMP-10表达，并且在患有各种关节病的患者的滑膜液样本中检测到MMP-10。外源性MMP-10显著增强了IL-1加OSM刺激的软骨的胶原溶解，并且MMP-10激活了前MMP-1、前MMP-8和前MMP-13。免疫组织化学显示，在IL-1加OSM诱导的关节炎模型的滑膜和软骨以及患病人类组织样本中存在MMP-10。
我们证实，在用促分解代谢刺激处理后，滑膜成纤维细胞和关节软骨细胞均表达MMP-10。此外，滑膜液中可检测到的MMP-10水平以及在患病关节组织中对这种蛋白酶的组织学检测强烈表明MMP-10在关节炎期间的软骨降解组中起作用。MMP-10超激活与软骨降解相关的原胶原酶的能力表明，这种激活代表了这种MMP促成关节炎中组织破坏的重要机制。
