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, Hansung Kim, Hong In Shin, Goo Taeg Oh, Hyun Seok Kim, Soo Young Lee

Research output: Contribution to journalArticle

8 Citations (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.

Original languageEnglish
Article number26186
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 May 18

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Osteoclasts
B-Lymphocytes
Proteins
Osteogenesis
Histone Deacetylases
Bone Remodeling
Metabolic Bone Diseases
Gene Deletion
Gene Expression
Bone and Bones
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Park, S. J., Huh, J. E., Shin, J., Park, D. R., Ko, R., Jin, G. R., ... Lee, S. Y. (2016). Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation. Scientific reports, 6, [26186]. https://doi.org/10.1038/srep26186
Park, So Jeong ; Huh, Jeong Eun ; Shin, Jihye ; Park, Doo Ri ; Ko, Ryeojin ; Jin, Gyu Rin ; Seo, Dong Hyun ; Kim, Hansung ; Shin, Hong In ; Oh, Goo Taeg ; Kim, Hyun Seok ; Lee, Soo Young. / Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation. In: Scientific reports. 2016 ; Vol. 6.
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Park, SJ, Huh, JE, Shin, J, Park, DR, Ko, R, Jin, GR, Seo, DH, Kim, H, Shin, HI, Oh, GT, Kim, HS & Lee, SY 2016, 'Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation', Scientific reports, vol. 6, 26186. https://doi.org/10.1038/srep26186

Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation. / Park, So Jeong; Huh, Jeong Eun; Shin, Jihye; Park, Doo Ri; Ko, Ryeojin; Jin, Gyu Rin; Seo, Dong Hyun; Kim, Hansung; Shin, Hong In; Oh, Goo Taeg; Kim, Hyun Seok; Lee, Soo Young.

In: Scientific reports, Vol. 6, 26186, 18.05.2016.

Research output: Contribution to journalArticle

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AU - Jin, Gyu Rin

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AU - Kim, Hansung

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AU - Lee, Soo Young

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