title: Serum amyloid A inhibits osteoclast differentiation to maintain macrophage function.
abstract: Serum amyloid A is an acute phase protein that is elevated under inflammatory conditions. Additionally, the serum levels of serum amyloid A are associated with the progression of inflammatory arthritis; thus, serum amyloid A might be involved in the regulation of osteoclast differentiation. In the present study, we examined the effects of serum amyloid A on osteoclast differentiation and function. When bone marrow-derived macrophages, as osteoclast precursors, were stimulated with serum amyloid A in the presence of M-CSF and receptor activator of nuclear factor-κB ligand, osteoclast differentiation and its bone-resorption activity were substantially inhibited. TLR2 was important in the inhibitory effect of serum amyloid A on osteoclast differentiation, because serum amyloid A stimulated TLR2. The inhibitory effect was absent in bone marrow-derived macrophages obtained from TLR2-deficient mice. Furthermore, serum amyloid A inhibited the expression of c-Fos and nuclear factor of activated T cells c1, which are crucial transcription factors for osteoclast differentiation, but prevented downregulation of IFN regulatory factor-8, a negative regulator of osteoclast differentiation. In contrast, serum amyloid A sustained the endocytic capacity of bone marrow-derived macrophages and their ability to induce the proinflammatory cytokines, IL-6, IL-1β, and TNF-α. Taken together, these results suggest that serum amyloid A, when increased by inflammatory conditions, inhibits differentiation of macrophages to osteoclasts, likely to maintain macrophage function for host defense.
authors.affiliation: *Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; and Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jiseon
authors.initials: J
authors.lastname: Kim
authors.affiliation: *Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; and Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: *Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; and Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
authors.forename: Ok-Jin
authors.initials: OJ
authors.lastname: Park
authors.affiliation: *Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; and Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.affiliation: *Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; and Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: *Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Korea; Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; and Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea shhan-mi@snu.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000276:immunology*; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
chemical_list: D016207:Cytokines; D016760:Proto-Oncogene Proteins c-fos; D000685:Serum Amyloid A Protein; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: IFN regulatory factor 8; NFATc1; TLR; c-Fos