Serum amyloid A inhibits RANKL-induced osteoclast formation.
- Author:
Eunseo OH
1
;
Ha Young LEE
;
Hak Jung KIM
;
Yoo Jung PARK
;
Jeong Kon SEO
;
Joon Seong PARK
;
Yoe Sik BAE
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: 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
- From:Experimental & Molecular Medicine 2015;47(11):e194-
- CountryRepublic of Korea
- Language:English
- 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.
