The role of CCAAT/enhancer binding protein (C/EBP)-alpha in osteogenesis of C3H10T1/2 cells induced by BMP-2.
The balance between osteogenesis and adipogenesis of mesenchymal stem cells is disrupted in various human diseases. Investigating the mechanisms that fine-tune this balance is of medical importance. Identification of potential target gene which can be used to study the relationship between them could be really helpful for this purpose. In the current study, we used C3H10T1/2 as model cells and through which two models of both osteogenesis induced by bone-morphogenetic protein (BMP)-2 and transdifferentiation from osteogenesis to adipogenesis were established. We investigated the role of CCAAT/enhancer binding protein (C/EBP)-alpha in these two systems. Then from epigenetic point of view, we elucidated the underlying molecular mechanisms preliminarily. The results showed that down-regulations of both C/EBP-alpha expression and its inducibility in response to insulin, fetal bovine serum, methylisobutylxanthine and dexamethasone (IFMD) adipogenic hormonal cocktail were observed in terminal stage of osteogenesis of C3H10T1/2 cells induced by BMP-2. And overexpression of C/EBP-alpha could lead to inhibition of osteogenesis differentiation and rescue attenuation of potential of adipogenic conversion in this process. Furthermore, we provided evidence that remarkable DNA hypermethylation and histones 3 and 4 hypoacetylation in -1286 bp/1065 bp promoter region of C/EBP-alpha were involved in both of down-regulations. Our data suggest that C/EBP-alpha functions as regulator in the balance between osteogenesis and adipogenesis of C3H10T1/2 cells and may be a therapeutic target.
Fan
Qiming
Q
Orthopaedic Cellular & Molecular Biology Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
Tang
Tingting
T
Department of Orthopaedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
Zhang
Xiaoling
X
Orthopaedic Cellular & Molecular Biology Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
Dai
Kerong
K
Department of Orthopaedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D010012:Osteogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D022763:CCAAT-Enhancer-Binding Protein-alpha; D017931:DNA Primers; D003907:Dexamethasone