IDENTIFICATION OF MEMBRANE-TYPE 1 MATRIX METALLOPROTEINASE AS A NOVEL THERAPEUTIC TARGET OF RHEUMATOID ARTHRITIS

类风湿关节炎(RA)是一种以软骨等关节组织破坏为主要病理特征的全身性自身免疫性疾病。我们最近的研究表明，一种细胞膜锚定的蛋白降解酶MT1-MMPs在RA的软骨侵蚀中起重要作用。我们推测，特异性抑制MT1-MMPs可能是一种潜在的RA治疗方法。我们建议通过评估在胶原诱导性关节炎(CIA)转基因小鼠中MT1-MMP抑制在RA进展中的作用来解决这一问题。我们还将分析MT1-MMP特异性抑制性抗体在CIA小鼠中的作用。这项工作的完成将使MT1-基质金属蛋白酶成为RA治疗的新靶点，这可能会导致未来新的RA治疗方法的发展。

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose key pathological features is destruction of joint tissues including cartilage. Our recent data indicated that a cell membrane-anchored protein degrading enzyme termed, MT1-MMP, plays an essential role in cartilage erosion in RA. We hypothesize that specific inhibition of MT1-MMP can be a potential RA treatment. We propose to address this by assessing the effect of MT1-MMP inhibition in RA progression in a collagen-induced arthritis (CIA) in transgenic mice that express a dominant negative inhibitor of MT1-MMP. We will also analyze the effect of a MT1-MMP-specific inhibitory antibody in mice with CIA. Completing the proposed work would establish MT1-MMP as a novel therapeutic target of RA treatment, which may lead into development of novel RA therapy in the future.