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G Protein‐Coupled Receptor 120 Signaling Negatively Regulates Osteoclast Differentiation, Survival, and Function
Author(s) -
Kim HyunJu,
Yoon HyeJin,
Kim Bo Kyung,
Kang Woo Youl,
Seong Sook Jin,
Lim MiSun,
Kim ShinYoon,
Yoon YoungRan
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25133
Subject(s) - osteoclast , microbiology and biotechnology , function (biology) , receptor , signal transduction , chemistry , biology , biochemistry
G protein‐coupled receptor 120 (GPR120) plays an important role in the regulation of inflammation and lipid metabolism. In this study, we investigated the role of GPR120 in osteoclast development and found that GPR120 regulates osteoclast differentiation, survival and function. We observed that GPR120 was highly expressed in osteoclasts compared to their precursors, bone marrow‐derived macrophages (BMMs). Activation of GPR120 by its ligand GW9508 suppressed receptor activator of NF‐ κB ligand (RANKL)‐induced osteoclast differentiation and the expression of nuclear factor of activated T cells c1 (NFATc1), a key modulator of osteoclastogenesis. GPR120 activation further inhibited the RANKL‐stimulated phosphorylation of IκBα and JNK. In addition to osteoclast differentiation, GPR120 activation increased the apoptosis of mature osteoclasts by inducing caspase‐3 and Bim expression. Activation of GPR120 also interfered with cell spreading and actin cytoskeletal organization mediated by M‐CSF but not by RANKL. Coincident with the impaired cytoskeletal organization, GPR120 activation blocked osteoclast bone resorbing activity. Furthermore, knockdown of GPR120 using small hairpin RNA abrogated all these inhibitory effects on osteoclast differentiation, survival, and function. Together, our findings identify GPR120 as a negative modulator of osteoclast development that may be an attractive therapeutic target for bone‐destructive diseases. J. Cell. Physiol. 231: 844–851, 2016. © 2015 Wiley Periodicals, Inc.