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

类风湿性关节炎（RA）是一种全身性自身免疫性疾病，其主要病理特征是包括软骨在内的关节组织的破坏。我们最近的数据表明，细胞膜锚定的蛋白降解酶称为，MT 1-MMP，在RA软骨侵蚀中起着至关重要的作用。我们推测特异性抑制MT 1-MMP可能是一种潜在的RA治疗方法。我们建议通过在表达MT 1-MMP显性负抑制剂的转基因小鼠中评估MT 1-MMP抑制在胶原诱导的关节炎（CIA）中RA进展中的作用来解决这一问题。我们还将分析MT 1-MMP特异性抑制抗体在CIA小鼠中的作用。该工作的完成将使MT 1-MMP成为RA治疗的新靶点，为将来RA治疗提供新的思路。

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.