title: Histone Acetyltransferase GCN5 Regulates Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting NF-κB.
abstract: As the most well-studied histone acetyltransferase (HAT) in yeast and mammals, general control nonderepressible 5 (GCN5) was documented to play essential roles in various developmental processes. However, little is known about its role in osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we detected the critical function of GCN5 in osteogenic commitment of MSCs. In this role, the HAT activity of GCN5 was not required. Mechanistically, GCN5 repressed nuclear factor kappa B (NF-κB)-dependent transcription and inhibited the NF-κB signaling pathway. The impaired osteogenic differentiation by GCN5 knockdown was blocked by inhibition of NF-κB. Most importantly, the expression of GCN5 was decreased significantly in the bone tissue sections of ovariectomized mice or aged mice. Collectively, these results may point to the GCN5-NF-κB pathway as a novel potential molecular target for stem cell mediated regenerative medicine and the treatment of metabolic bone diseases such as osteoporosis.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Chanyuan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.|National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010012:Osteogenesis; D010024:Osteoporosis / Q000378:metabolism; D015398:Signal Transduction; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D016328:NF-kappa B; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
keywords: GCN5; MSCS; NF-κB; OSTEOGENIC DIFFERENTIATION; OSTEOPOROSIS