Exp Mol Med.
2015 Nov;47(11):e194. 10.1038/emm.2015.83.
Serum amyloid A inhibits RANKL-induced osteoclast formation
- Affiliations
-
- 1Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea. yoesik@skku.edu
- 2Mitochondria Hub Regulation Center, Dong-A University, Busan, Republic of Korea.
- 3UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
- 4Department of Hematology and Oncology, Ajou University School of Medicine, Suwon, Republic of Korea.
- 5Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
- KMID: 2359881
- DOI: http://doi.org/10.1038/emm.2015.83
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.
MeSH Terms
-
Adenosine Triphosphate/metabolism
Animals
Cell Differentiation
Cell Line
Gene Expression Regulation, Developmental
Humans
Macrophages/*cytology/metabolism
Mice
Osteoclasts/*cytology/metabolism
RANK Ligand/*metabolism
Receptor, Macrophage Colony-Stimulating Factor/genetics
Receptors, Formyl Peptide/metabolism
Serum Amyloid A Protein/*metabolism
Toll-Like Receptor 2/metabolism
Toll-Like Receptor 4/metabolism
Adenosine Triphosphate
RANK Ligand
Receptor, Macrophage Colony-Stimulating Factor
Receptors, Formyl Peptide
Serum Amyloid A Protein
Toll-Like Receptor 2
Toll-Like Receptor 4
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