Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan;
J Appl Physiol (1985). 2013 Sep;115(6):884-91. doi: 10.1152/japplphysiol.00137.2013. Epub 2013 May 2.
The extracellular matrix (ECM) of skeletal muscle and tendon is composed of different types of collagen molecules that play important roles in the transmission of forces throughout the body, and in the repair and regeneration of injured tissues. Fibroblasts are the primary cells in muscle and tendon that maintain, repair, and modify the ECM in response to mechanical loading, injury, and inactivity. Matrix metalloproteinases (MMPs) are enzymes that digest collagen and other structural molecules, which are synthesized and excreted by fibroblasts. MMPs are required for baseline ECM homeostasis, but disruption of MMP regulation due to injury or disease can alter the normal ECM architecture and prevent proper force transmission. Chronic injuries and diseases of muscles and tendons can be severely debilitating, and current therapeutic modalities to enhance healing are quite limited. This review will discuss the mechanobiology of MMPs, and the potential use of MMP inhibitors to improve the treatment of injured and diseased skeletal muscle and tendon tissue.
骨骼肌和肌腱的细胞外基质(ECM)由不同类型的胶原蛋白分子组成,这些分子在体内力的传递以及受伤组织的修复和再生中起着重要作用。成纤维细胞是肌肉和肌腱中的主要细胞,它们通过机械加载、损伤和不活动来维持、修复和修饰 ECM。基质金属蛋白酶(MMPs)是消化胶原蛋白和其他结构分子的酶,这些酶由成纤维细胞合成和分泌。MMPs 是 ECM 基础稳态所必需的,但由于损伤或疾病导致 MMP 调节的破坏可能会改变正常的 ECM 结构,并阻止正常的力传递。肌肉和肌腱的慢性损伤和疾病可能会严重致残,目前增强愈合的治疗方法相当有限。本综述将讨论 MMP 的机械生物学,以及 MMP 抑制剂在改善受伤和患病的骨骼肌和肌腱组织治疗中的潜在用途。