Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation

So Jeong Park, Jeong Eun Huh, Jihye Shin, Doo Ri Park, Ryeojin Ko, Gyu Rin Jin, Dong Hyun Seo, Han Sung Kim, Hong In Shin, Goo Taeg Oh, Hyun Seok Kim, Soo Young Lee

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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.

Original languageEnglish
Article number26186
JournalScientific Reports
StatePublished - 18 May 2016

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (No. 2013R1A2A1A05005153; No. 2012R1A5A1048236; No. 2012M3A9C5048708; No. 2012R1A3A2026454; No. 2015R1D1A4A01020104).


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