Cawston T E
Rheumatology Research Unit, Addenbrookes Hospital, Cambridge, UK.
Br Med Bull. 1995 Apr;51(2):385-401. doi: 10.1093/oxfordjournals.bmb.a072968.
The primary agents responsible for cartilage and bone destruction in joint diseases are active proteinases degrading collagen and proteoglycan. All four main classes of proteolytic enzymes are involved in either the normal turnover of connective tissue or its pathological destruction. These proteinases are made by different cells found within the joints. Both extracellular and intracellular pathways exist and individual enzymes can be inhibited by specific proteinaceous inhibitors that block their activity. Recent research has implicated the matrix metalloproteinases (MMPs) in many of the processes involved in joint diseases. Conventional treatments do little to affect the underlying disease processes and recently the use of proteinase inhibitors has been suggested as a new therapeutic approach. Inhibitors of proteinases can prevent the destruction of animal cartilage in model systems and future patient trials will test the effectiveness of these compounds in vivo.
在关节疾病中,导致软骨和骨破坏的主要因素是能够降解胶原蛋白和蛋白聚糖的活性蛋白酶。所有四类主要的蛋白水解酶都参与结缔组织的正常更新或其病理破坏过程。这些蛋白酶由关节内发现的不同细胞产生。细胞外和细胞内途径均存在,并且个别酶可被阻断其活性的特定蛋白质抑制剂所抑制。最近的研究表明基质金属蛋白酶(MMPs)参与了许多关节疾病相关的过程。传统治疗对潜在的疾病进程影响甚微,最近有人提出使用蛋白酶抑制剂作为一种新的治疗方法。蛋白酶抑制剂可以在模型系统中防止动物软骨的破坏,未来的患者试验将测试这些化合物在体内的有效性。