McCarthy G M, Mitchell P G, Cheung H S
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Arthritis Rheum. 1991 Aug;34(8):1021-30. doi: 10.1002/art.1780340812.
Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathies that are characterized by synovial proliferation and digestion of articular collagenous structures. BCP crystals are potent mitogens, which may account for this proliferation. The role of collagenase in articular degradation is controversial because, despite the massive loss of collagen, no studies have confirmed collagenolytic activity in synovial fluid, as originally reported. We investigated collagenase messenger RNA induction and enzyme activity in human foreskin fibroblasts proliferating in response to stimulation with BCP crystals, and analyzed the associated secreted proteins. Northern blots revealed a dose-dependent accumulation of collagenase message, evident by 4 hours and continuing to at least 36 hours, in BCP-stimulated cultures. One- and 2-dimensional polyacrylamide gel electrophoresis of conditioned media from BCP crystal-stimulated cultures revealed the selective induction of 2 proteins with molecular weight and pI values consistent with those of collagenase. Increased enzyme activity was also found. Thus, the mitogenic response of fibroblasts to BCP crystals is accompanied by collagenase induction and secretion, supporting the hypothesis that they act as a mediator of joint destruction in BCP crystal-associated arthropathies.
滑膜液碱性磷酸钙（BCP）晶体与严重的破坏性关节病相关，其特征为滑膜增生和关节胶原结构的消解。BCP晶体是强效有丝分裂原，这可能是导致这种增生的原因。胶原酶在关节降解中的作用存在争议，因为尽管胶原大量丢失，但正如最初报道的那样，尚无研究证实滑膜液中有胶原olytic活性。我们研究了在BCP晶体刺激下增殖的人包皮成纤维细胞中胶原酶信使核糖核酸的诱导和酶活性，并分析了相关的分泌蛋白。Northern印迹显示，在BCP刺激的培养物中，胶原酶信使核糖核酸呈剂量依赖性积累，4小时时明显，至少持续到36小时。对BCP晶体刺激培养物的条件培养基进行一维和二维聚丙烯酰胺凝胶电泳，发现选择性诱导出2种蛋白质，其分子量和等电点值与胶原酶一致。还发现酶活性增加。因此，成纤维细胞对BCP晶体的有丝分裂反应伴随着胶原酶的诱导和分泌，支持了它们在BCP晶体相关关节病中作为关节破坏介质的假说。
