title: HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis.
abstract: The bone-resorbing osteoclast (OC) is essential for bone homeostasis, yet deregulation of OCs contributes to diseases such as osteoporosis, osteopetrosis, and rheumatoid arthritis. Here we show that histone deacetylase 2 (HDAC2) is a key positive regulator during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Bone marrow macrophages (BMMs) showed increased HDAC2 expression during osteoclastogenesis. HDAC2 overexpression enhanced, whereas HDAC2 deletion suppressed osteoclastogenesis and bone resorption using lentivirus infection. Mechanistically, upon RANKL activation, HDAC2 activated Akt; Akt directly phosphorylates and abrogates Forkhead box protein O1 (FoxO1), which is a negative regulator during osteoclastogenesis through reducing reactive oxygen species. HDAC2 deletion in BMMs resulted in decreased Akt activation and increased FoxO1 activity during osteoclastogenesis. In conclusion, HDAC2 activates Akt thus suppresses FoxO1 transcription results in enhanced osteoclastogenesis. Our data imply the potential value of HDAC2 as a new target in regulating osteoclast differentiation and function.
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ce
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Fei
authors.initials: F
authors.lastname: Kang
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Quan
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Tianyong
authors.initials: T
authors.lastname: Hou
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China; and dongshiwu@tmmu.edu.cn.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Dong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2
keywords: Akt; FoxO1; HDAC2; bone resorption; osteoclasts