| First Author | Omata Y | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 6 | Pages | e0157992 |
| PubMed ID | 27336669 | Mgi Jnum | J:322376 |
| Mgi Id | MGI:6252929 | Doi | 10.1371/journal.pone.0157992 |
| Citation | Omata Y, et al. (2016) Identification of Nedd9 as a TGF-beta-Smad2/3 Target Gene Involved in RANKL-Induced Osteoclastogenesis by Comprehensive Analysis. PLoS One 11(6):e0157992 |
| abstractText | TGF-ss is a multifunctional cytokine that is involved in cell proliferation, differentiation and function. We previously reported an essential role of the TGF-ss -Smad2/3 pathways in RANKL-induced osteoclastogenesis. Using chromatin immunoprecipitation followed by sequencing, we comprehensively identified Smad2/3 target genes in bone marrow macrophages. These genes were enriched in the gene population upregulated by TGF-ss and downregulated by RANKL. Recent studies have revealed that histone modifications, such as trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3), critically regulate key developmental steps. We identified Nedd9 as a Smad2/3 target gene whose histone modification pattern was converted from H3K4me3(+)/H3K4me27(+) to H3K4me3(+)/H3K4me27(-) by TGF-ss. Nedd9 expression was increased by TGF-ss and suppressed by RANKL. Overexpression of Nedd9 partially rescued an inhibitory effect of a TGF-ss inhibitor, while gene silencing of Nedd9 suppressed RANKL-induced osteoclastogenesis. RANKL-induced osteoclastogenesis were reduced and stimulatory effects of TGF-ss on RANKL-induced osteoclastogenesis were partially abrogated in cells from Nedd9-deficient mice although knockout mice did not show abnormal skeletal phenotypes. These results suggest that Nedd9 is a Smad2/3 target gene implicated in RANKL-induced osteoclastogenesis. |
