title: Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation.
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.
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.|The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: So Jeong
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.|The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Huh
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.|The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.|The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Doo Ri
authors.initials: DR
authors.lastname: Park
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.|The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Ryeojin
authors.initials: R
authors.lastname: Ko
authors.affiliation: The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.|Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Gyu-Rin
authors.initials: GR
authors.lastname: Jin
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Institute of Medical Engineering, Yonsei University, Wonju, Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Seo
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Institute of Medical Engineering, Yonsei University, Wonju, Korea.
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: IHBR, Department of Oral Pathology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.affiliation: The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.|Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Life Science, Ewha Womans University, Seoul 120-750, Korea.|The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D037761:Sirtuins / Q000378:metabolism*
chemical_list: C513258:Prdm1 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1; C501860:Sirt6 protein, mouse; D037761:Sirtuins