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

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Abstract

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.

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Acknowledgments

“The work was supported by Korea Research Foundation Grant (KRF-2007-314-E00111) and the Fund of Chonbuk National University Hospital Research Institute of Clinical Medicine.”

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, #634-18, Geumam-Dong, Deokjin-Gu, Chonju, Jeonbuk, 561-712, South Korea

    Hee-Jin Yun, Eun-Gyeong Lee & Wan-Hee Yoo

  2. Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Gyungnam, 660-751, South Korea

    Sang-Il Lee

  3. Department of Pharmacology, Chonbuk National University Medical School, Chonju, Jeonbuk, 561-712, South Korea

    Han-Jung Chae

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  1. Hee-Jin Yun
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  2. Eun-Gyeong Lee
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  5. Wan-Hee Yoo
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Correspondence to Wan-Hee Yoo.

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Yun, HJ., Lee, EG., Lee, SI. et al. Adrenomedullin inhibits MAPK pathway-dependent rheumatoid synovial fibroblast-mediated osteoclastogenesis by IL-1 and TNF-α. Rheumatol Int 29, 1161–1168 (2009). https://doi.org/10.1007/s00296-008-0832-0

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  • DOI: https://doi.org/10.1007/s00296-008-0832-0

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