Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue.
Academic Article
Overview
abstract
OBJECTIVE: The aim of the study was to analyze the expression of the disintegrin metalloproteinase MDC15 (metargidin, or ADAM15) at the messenger RNA (mRNA) and protein levels in synovial tissue from osteoarthritis (OA) and rheumatoid arthritis (RA) patients compared with normal specimens. METHODS: Conventional immunohistochemistry and confocal laser scanning microscopy of immunofluorescently stained sections, as well as in situ hybridization experiments and reverse transcription-polymerase chain reaction were performed for analyses of MDC15 expression on normal, OA, and RA synovial tissue specimens. RESULTS: In normal synovium, MDC15 expression was detectable at a very low level. MDC15 expression was considerably increased in OA-derived tissue samples, 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 MDC15. Moreover, a very strong expression of MDC15 was also found in CD138+ plasma cells in all RA tissues as well as in OA specimens that contained areas of mononuclear cell infiltrates. CD20+ B cells and CD4+ and CD8+ T cells, however, did not exhibit expression of MDC15, either in the synovial tissue in situ or in preparations of circulating lymphocytes made from the peripheral blood of RA patients or healthy controls. CONCLUSION: Our results demonstrate high levels of MDC15 expression in macrophage-like and fibroblast-like synoviocytes as well as in plasma cells as a histologic feature most prominent in RA synovial tissue compared with normal or OA synovial tissue. This suggests a potential role of MDC15 in the pathogenesis of cartilage destruction in inflammatory joint disease.
