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Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue
B B Böhm1, T Aigner, C P Blobel
1University of Erlangen-Nuremberg, Erlangen, Germany.
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.
Insights
Disintegrin metalloproteinase MDC15 (ADAM15) is highly expressed in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue, particularly in macrophages, fibroblasts, and plasma cells. This suggests a role for MDC15 in inflammatory joint disease pathogenesis.
Area of Science:
- Rheumatology
- Cell Biology
- Molecular Biology
Background:
- Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory joint diseases characterized by synovial tissue changes.
- Disintegrin metalloproteinases, including MDC15 (ADAM15), are implicated in tissue remodeling and inflammation.
Purpose of the Study:
- To investigate the expression of MDC15 (metargidin, ADAM15) at mRNA and protein levels in synovial tissue from OA and RA patients compared to normal controls.
Main Methods:
- Immunohistochemistry and confocal microscopy were used to analyze MDC15 protein expression.
- In situ hybridization and RT-PCR were employed for mRNA expression analysis.
- Synovial tissue samples from normal, OA, and RA patients were examined.
Main Results:
- MDC15 expression was low in normal synovium, increased in OA, and highest in RA lining layers.
- MDC15 was expressed in macrophage-like (CD68+) and fibroblast-like (CD68-) synoviocytes.
- Strong MDC15 expression was observed in plasma cells (CD138+) in RA and OA tissues with infiltrates.
- MDC15 was not detected in CD20+ B cells or CD4+/CD8+ T cells.
Conclusions:
- MDC15 is highly expressed in synoviocytes and plasma cells, with prominent expression in RA synovial tissue.
- These findings suggest a potential role for MDC15 in the pathogenesis of cartilage destruction in inflammatory joint diseases.

