| First Author | Park SJ | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 26186 | PubMed ID | 27189179 |
| Mgi Jnum | J:254107 | Mgi Id | MGI:6101614 |
| Doi | 10.1038/srep26186 | Citation | Park SJ, et al. (2016) Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation. Sci Rep 6:26186 |
| abstractText | Global deletion of the gene encoding a nuclear histone deacetylase sirtuin 6 (Sirt6) in mice leads to osteopenia with a low bone turnover due to impaired bone formation. But whether Sirt6 regulates osteoclast differentiation is less clear. Here we show that Sirt6 functions as a transcriptional regulator to directly repress anti-osteoclastogenic gene expression. Targeted ablation of Sirt6 in hematopoietic cells including osteoclast precursors resulted in increased bone volume caused by a decreased number of osteoclasts. Overexpression of Sirt6 led to an increase in osteoclast formation, and Sirt6-deficient osteoclast precursor cells did not undergo osteoclast differentiation efficiently. Moreover, we showed that Sirt6, induced by RANKL-dependent NFATc1 expression, forms a complex with B lymphocyte-induced maturation protein-1 (Blimp1) to negatively regulate expression of anti-osteoclastogenic gene such as Mafb. These findings identify Sirt6 as a novel regulator of osteoclastogenesis by acting as a transcriptional repressor. |
