基质金属蛋白酶13在软骨重塑和关节炎中的研究进展

Advances in matrix metalloproteinase 13 in cartilage remodeling and arthritis

关节炎是一种常见的慢性疾病,其主要特征是关节软骨的破坏和周围组织的慢性炎症。关节炎的发病机制比较复杂,受多种因素影响。近年来研究发现,关节软骨中基质金属蛋白酶(MMPs)的增加,是造成软骨细胞外基质(ECM)降解,从而引起软骨退化的重要原因。其中,MMP-13是促使其降解的主要酶,它能不可逆地降解Ⅱ型胶原,从而造成关节软骨的破坏。MMP-13可受到多种因素的影响,如IL-1β、TNF-α、Runx2可以诱导MMP-13的表达。MMP-13启动子区域的低甲基化也会诱导其表达,但可以通过抑制组蛋白乙酰化来降低其表达。除此之外,微小RNA也可以通过基因调控来降低MMP-13的表达。MMP-13的上调会导致软骨的退化,进而促进关节炎的进程。综上所述,MMP-13可作为关节炎中重要的治疗靶点,该文将对MMP-13在关节炎中的作用及其调节机制作一综述。

Arthritis is a common chronic disease characterized by the destruction of joint cartilage and inflammation in the surrounding tissues.Although it is known that the pathogenesis of arthritis is influenced by a series of factors,the underlying mechanisms remain unclarified.Recently,increasing attention has been paid to the increase of matrix metalloproteinases(MMPs)in articular cartilage,resulting in an inevitable degradation of cartilage and extracellular matrix(ECM).MMP-13,the major functioning enzyme during arthritis development,plays a vital role in the cartilage destruction,thus contributing to the decomposition of type II collagen irreversibly.A variety of cellular cytokines such as IL-1βand TNF-α,and Runx2 are assumed to affect the expression of MMP-13 in chondrocytes.The hypomethylation of the promoter region of the MMP-13 may induce its expression,while it can be reduced by inhibiting histone acetylation.Meanwhile,microRNA can reduce the expression of MMP-13.In conclusion,MMP-13 can be used as an important therapeutic target in arthritis.In this review,we focus on the role of MMP-13 in arthritis and its underlying regulatory mechanisms.