title: Serum amyloid A inhibits RANKL-induced osteoclast formation.
abstract: When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Eunseo
authors.initials: E
authors.lastname: Oh
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.|Mitochondria Hub Regulation Center, Dong-A University, Busan, Republic of Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Hak Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Yoo Jung
authors.initials: YJ
authors.lastname: Park
authors.affiliation: UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Seo
authors.affiliation: Department of Hematology and Oncology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.|Mitochondria Hub Regulation Center, Dong-A University, Busan, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D053245:RANK Ligand; D044042:Receptors, Formyl Peptide; D000685:Serum Amyloid A Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C481578:formyl peptide receptor 2, mouse; D000255:Adenosine Triphosphate; D016186:Receptor, Macrophage Colony-Stimulating Factor