Adrenomedullin inhibits MAPK pathway-dependent rheumatoid synovial fibroblast-mediated osteoclastogenesis by IL-1 and TNF-[alpha]

• Published in: Rheumatology international 2009-08, Vol.29 (10), p.1161
• Main Authors: Yun, Hee-jin, Lee, Eun-gyeong, Lee, Sang-il, Chae, Han-jung, Yoo, Wan-hee
• Format: Article
• Language: English
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-008-0832-0

The objective of this study is to determine the effects of adrenomedullin (AM) on IL-1- and TNF-α-induced rheumatoid synovial fibroblasts (RASFs)-mediated osteoclastogenesis. The formation of osteoclasts in co-cultures of RASFs and peripheral blood mononuclear cells was evaluated by tartrate-resistant acid phosphatase and resorption pit formation assay. The expression of RANKL, OPG, p-ERK, p-p38, and p-JNK was examined by immunoblotting and quantitative reverse transcription-polymerase chain reaction. AM (1-52) inhibits IL-1- and TNF-α-induced RASFs-mediated osteoclastogenesis. AM affected IL-1-, TNF-α-induced RANKL and OPG expression in RASFs. AM also inhibits IL-1 and TNF-α-induced phosphorylation of ERK-1/2, p38 MAPK, and JNK. Inhibitor of AM (AM 22-52) inhibits the effects of AM on the osteoclastogenesis. These results suggest that AM might be involved in the inflammatory cytokines-mediated osteoclastogenesis and thus bone damage, and indicate that it can be a new therapeutic strategy against joint destruction in RA.[PUBLICATION ABSTRACT]