Adrenomedullin inhibits MAPK pathway-dependent rheumatoid synovial fibroblast-mediated osteoclastogenesis by IL-1 and TNF-alpha
Autor: | Eun-Gyeong Lee, Han-Jung Chae, Wan-Hee Yoo, Sang-Il Lee, Hee-Jin Yun |
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Rok vydání: | 2008 |
Předmět: |
musculoskeletal diseases
MAPK/ERK pathway medicine.medical_specialty Time Factors p38 mitogen-activated protein kinases Immunology Acid Phosphatase Arthritis Osteoclasts Peripheral blood mononuclear cell Arthritis Rheumatoid Adrenomedullin Rheumatology Internal medicine medicine Immunology and Allergy Humans RNA Messenger Fibroblast Tartrate-resistant acid phosphatase biology business.industry Tartrate-Resistant Acid Phosphatase Tumor Necrosis Factor-alpha RANK Ligand Synovial Membrane Osteoprotegerin Fibroblasts medicine.disease Coculture Techniques Recombinant Proteins Isoenzymes Endocrinology medicine.anatomical_structure RANKL Cancer research biology.protein Leukocytes Mononuclear Mitogen-Activated Protein Kinases business Interleukin-1 |
Zdroj: | Rheumatology international. 29(10) |
ISSN: | 1437-160X |
Popis: | The objective of this study is to determine the effects of adrenomedullin (AM) on IL-1- and TNF-alpha-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-alpha-induced RASFs-mediated osteoclastogenesis. AM affected IL-1-, TNF-alpha-induced RANKL and OPG expression in RASFs. AM also inhibits IL-1 and TNF-alpha-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. |
Databáze: | OpenAIRE |
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