TY - JOUR
T1 - FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2
AU - Park, Min Young
AU - Kim, Hyung Sik
AU - Lee, Mingyu
AU - Park, Byunghyun
AU - Lee, Ha Young
AU - Cho, Eun Bee
AU - Seong, Jae Young
AU - Bae, Yoe Sik
N1 - Funding Information:
This study was supported by grant of the National Research Foundation of Korea [2015R1A2A1A10054567 (YB)].
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85034064679&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-15586-0
DO - 10.1038/s41598-017-15586-0
M3 - Article
C2 - 29138422
AN - SCOPUS:85034064679
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 15575
ER -