title: Dynamic and distinct histone modifications of osteogenic genes during osteogenic differentiation.
abstract: Many skeletal diseases have common pathological phenotype of defective osteogenesis of bone marrow stromal cells (BMSCs), in which histone modifications play an important role. However, few studies have examined the dynamics of distinct histone modifications during osteogenesis. In this study, we examined the dynamics of H3K9/K14 and H4K12 acetylation; H3K4 mono-, di- and tri-methylation; H3K9 di-methylation and H3K27 tri-methylation in osteogenic genes, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase, bone sialoprotein and osteocalcin, during C3H10T1/2 osteogenesis. H3 and H4 acetylation and H3K4 di-methylation were elevated, and H3K9 di-methylation and H3K27 tri-methylation were reduced in osteogenic genes during C3H10T1/2 osteogenesis. C3H10T1/2 osteogenesis could be modulated by altering the patterns of H3 and H4 acetylation and H3K27 tri-methylation. In a glucocorticoid-induced osteoporosis mouse model, we observed the attenuation of osteogenic potential of osteoporotic BMSCs in parallel with H3 and H4 hypo-acetylation and H3K27 hyper-tri-methylation in Runx2 and Osx genes. When H3 and H4 acetylation was elevated, and H3K27 tri-methylation was reduced, the attenuated osteogenic potential of osteoporotic BMSCs was rescued effectively. These observations provide a deeper insight into the mechanisms of osteogenic differentiation and the pathophysiology of osteoporosis and can be used to design new drugs and develop new therapeutic methods to treat skeletal diseases.
authors.affiliation: Department of Orthopedics, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;
authors.forename: Yong-Xing
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, China; and.
authors.forename: Hai-Lang
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;
authors.forename: He
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Orthopedics, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China chillow@163.com.
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; sawboneszhao@163.com.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zhao
mesh_terms: D000107:Acetylation; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001847:Bone Diseases / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D053495:Osteopontin / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D006657:Histones; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; C506896:Spp1 protein, mouse; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase
keywords: bone marrow stromal cells; epigenetics; histone modification; osteogenesis; osteoporosis