| First Author | Omata Y | Year | 2015 |
| Journal | J Bone Miner Res | Volume | 30 |
| Issue | 5 | Pages | 869-77 |
| PubMed ID | 25431176 | Mgi Jnum | J:315542 |
| Mgi Id | MGI:6829194 | Doi | 10.1002/jbmr.2418 |
| Citation | Omata Y, et al. (2015) Genomewide comprehensive analysis reveals critical cooperation between Smad and c-Fos in RANKL-induced osteoclastogenesis. J Bone Miner Res 30(5):869-77 |
| abstractText | We have previously reported that transforming growth factor beta (TGF-beta) plays an essential role in receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis. However, the detailed underlying molecular mechanisms still remain unclear. Formaldehyde-assisted isolation of regulatory elements (FAIRE) and chromatin immunoprecipitation (ChIP) followed by sequencing (FAIRE-seq and ChIP-seq) analyses indicated the cooperation of Smad2/3 with c-Fos during osteoclastogenesis. Biochemical analysis and immunocytochemical analysis revealed that physical interaction between Smad2/3 and c-Fos is required for their nuclear translocation. The gene expression of nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1), a key regulator of osteoclastogenesis, was regulated by RANKL and TGF-beta, and c-Fos binding to open chromatin sites was suppressed by inhibition of TGF-beta signaling by SB431542. Conversely, Smad2/3 binding to Nfatc1 was impaired by c-Fos deficiency. These results suggest that TGF-beta regulates RANKL-induced osteoclastogenesis through reciprocal cooperation between Smad2/3 and c-Fos. |
