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Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation

Title
Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation
Authors
Park S.J.Huh J.-E.Shin J.Park D.R.Ko R.Jin G.-R.Seo D.-H.Kim H.-S.Shin H.-I.Oh G.T.Kim H.S.Lee S.Y.
Ewha Authors
이수영오구택김현석허정은
SCOPUS Author ID
이수영scopus; 오구택scopus; 김현석scopus; 허정은scopus
Issue Date
2016
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 6
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.1038/srep26186
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자연과학대학 > 생명과학전공 > Journal papers
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