Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue

Objective. The aim of the study was to analyze the expression of the disint egrin metalloproteinase MDC15 (metargidin, or ADAM15) at the messenger RNA (mRNA) and protein levels in synovial tissue from osteoarthritis (OA) and r heumatoid arthritis (RA) patients compared with normal specimens. Methods. Conventional immunohistochemistry and confocal laser scanning micr oscopy of immunofluorescently stained sections, as well as in situ hybridiz ation experiments and reverse transcription-polymerase chain reaction were performed for analyses of MDC15 expression on normal, OA, and RA synovial t issue specimens. Results. In normal synovium, MDC15 expression was detectable at a very low level. MDC15 expression was considerably increased in OA-derived tissue sam ples, whereas a maximum of signal intensity for MDC15 mRNA and protein was seen in the RA lining layer. The CD68+ macrophage-like synoviocytes (type A ) and the CD68- fibroblast-like synoviocytes (type B) were positive for MDC 15. Moreover, a very strong expression of MDC15 was also found in CD138+ pl asma cells in all RA tissues as well as in OA specimens that contained area s of mononuclear cell infiltrates. CD20+ B cells and CD4+ and CD8+ T cells, however, did not exhibit expression of MDC15, either in the synovial tissu e in situ or in preparations of circulating lymphocytes made from the perip heral blood of RA patients or healthy controls. Conclusion. Our results demonstrate high levels of MDC15 expression in macr ophage-like and fibroblast-like synoviocytes as well as in plasma cells as a histologic feature most prominent in RA synovial tissue compared with nor mal or OA synovial tissue. This suggests a potential role of MDC15 in the p athogenesis of cartilage destruction in inflammatory joint disease.