| First Author | Park MY | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 15575 |
| PubMed ID | 29138422 | Mgi Jnum | J:345533 |
| Mgi Id | MGI:6110221 | Doi | 10.1038/s41598-017-15586-0 |
| Citation | Park MY, et al. (2017) FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2. Sci Rep 7(1):15575 |
| abstractText | 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. |
