Characterization of collagenase 3 (Matrix metalloproteinase 13) messenger RNA expression in the synovial membrane and synovial fibroblasts of patients with rheumatoid arthritis

Objective, To study the localization and cell type-specific expression of c ollagenase 3 messenger RNA (mRNA) in the synovial membrane, its regulation in primary synovial fibroblasts, and the correlation with systemic markers of inflammation and radiographic damage in rheumatoid arthritis (RA), Methods, The expression of collagenase 3 mRNA was characterized by Northern blot analysis, reverse transcriptase-polymerase chain reaction, and in sit u hybridization, Immunohistochemical detection of cell type-specific antige ns was used in combination with in situ hybridization of collagenase 3 mRNA to characterize the cellular origin of collagenase 3 mRNA expression. Results. Collagenase 3 mRNA was detected in synovial membrane specimens of 21 of 36 RA patients (58%) and correlated with an increase in erythrocyte s edimentation rate (P < 0.05) and C-reactive protein levels (P < 0.005). Col lagenase 3 mRNA was localized in fibroblast-like cells of the lining and su blining layers, and at the synovial membrane-cartilage interface, Four of 1 0 primary synovial fibroblast cell cultures showed basal expression of coll agenase 3 mRNA, which was stimulated 2-4-fold upon interleukin-lp or tumor necrosis factor a treatment and, in contrast to interstitial collagenase mR NA, 5-10-fold by increasing the intracellular level of cAMP, The stimulatio n by cAMP analogs was completely abolished by protein kinase A inhibitors. Conclusion. Some RA patients show collagenase 3 mRNA expression in the syno vial membrane, which correlates with elevated levels of systemic markers of inflammation in these patients. In synovial fibroblasts, the expression of collagenase 3 and interstitial collagenase mRNA is differentially regulate d by distinct protein kinase signal transduction pathways.