BASIC CALCIUM-PHOSPHATE CRYSTALS INDUCE SYNTHESIS AND SECRETION OF 92KDA GELATINASE (GELATINASE-B MATRIX-METALLOPROTEASE-9) IN HUMAN FIBROBLASTS

Objective-Synovial fluid basic calcium phosphate (BCP) crystals are as sociated with severe joint degeneration accompanied by synovial hypert rophy. The metalloprotease 92 kDa gelatinase (MMP-9) has been implicat ed in the degradation of extracellular matrix in osteoarthritis, but t he ability of BCP crystals to induce gelatinase in human fibroblasts o r in adult porcine chondrocytes has not previously been studied. The h ypothesis that the mitogenic response to BCP crystals is accompanied b y induction and secretion of MMP-9 was studied. Methods-MMP-9 messenge r RNA (mRNA) was detected by northern blot and reverse transcription-p olymerase chain reaction (RT-PCR). Gelatinase secretion was identified by western blot and zymography of conditioned media. Results-BCP crys tals caused a concentration dependent induction of MMP-9 mRNA accumula tion and protein secretion in human fibroblasts but not in adult porci ne chondrocytes. Conclusion-BCP crystals induce MMP-9 production by HF but not adult porcine chondrocytes. Fibroblast MMP-9 may be an import ant mediator of the joint destruction associated with synovial fluid B CP crystals.