FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2

Min Young Park, Hyung Sik Kim, Mingyu Lee, Byunghyun Park, Ha Young Lee, Eun Bee Cho, Jae Young Seong, Yoe Sik Bae

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Osteoclasts can be differentiated from bone marrow-derived macrophages (BMDM). They play a key role in bone resorption. Identifying novel molecules that can regulate osteoclastogenesis has been an important issue. In this study, we found that FAM19A5, a neurokine or brain-specific chemokine, strongly stimulated mouse BMDM, resulting in chemotactic migration and inhibition of RANKL-induced osteoclastogenesis. Expression levels of osteoclast-related genes such as RANK, TRAF6, OSCAR, TRAP, Blimp1, c-fos, and NFATc1 were markedly decreased by FAM19A5. However, negative regulators of osteoclastogenesis such as MafB and IRF-8 were upregulated by FAM19A5. FAM19A5 also downregulated expression levels of RANKL-induced fusogenic genes such as OC-STAMP, DC-STAMP, and Atp6v0d2. FAM19A5-induced inhibitory effect on osteoclastogenesis was significantly reversed by a formyl peptide receptor (FPR) 2 antagonist WRW4 or by FPR2-deficiency, suggesting a crucial role of FPR2 in the regulation of osteoclastogenesis. Collectively, our results suggest that FAM19A5 and its target receptor FPR2 can act as novel endogenous ligand/receptor to negatively regulate osteoclastogenesis. They might be regarded as potential targets to control osteoclast formation and bone disorders.

Original languageEnglish
Article number15575
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Formyl Peptide Receptor
Osteoclasts
Chemokines
Osteogenesis
Brain
TNF Receptor-Associated Factor 6
Macrophages
Bone Resorption
Genes
Down-Regulation
Ligands

ASJC Scopus subject areas

  • General

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FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2. / Park, Min Young; Kim, Hyung Sik; Lee, Mingyu; Park, Byunghyun; Lee, Ha Young; Cho, Eun Bee; Seong, Jae Young; Bae, Yoe Sik.

In: Scientific Reports, Vol. 7, No. 1, 15575, 01.12.2017.

Research output: Contribution to journalArticle

Park, Min Young ; Kim, Hyung Sik ; Lee, Mingyu ; Park, Byunghyun ; Lee, Ha Young ; Cho, Eun Bee ; Seong, Jae Young ; Bae, Yoe Sik. / FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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