Open AccessThe mitogenic response to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase in human fibroblasts
Author(s) -
McCarthy Geraldine M.,
Mitchell Peter G.,
Cheung Herman S.
Publication year - 1991
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780340812
Subject(s) - secretion , collagenase , stimulation , calcium , endocrinology , medicine , microbiology and biotechnology , chemistry , biology , biochemistry , enzyme
Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthro‐pathies 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 flbroblasts 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.