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The role of CCAAT/enhancer binding protein (C/EBP) alpha in osteogenesis of C3H10T1/2 cells induced by BMP-2.
Qiming Fan a , Tingting Tang b , Xiaoling Zhang a , Kerong Dai b,#
a Orthopaedic Cellular & Molecular Biology Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai JiaoTong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, People's Republic of China b Department of Orthopaedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China
ABSTRACT
The balance between osteogenesis and adipogenesis of MSCs 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 BMP-2 and transdifferentiation from osteogenesis to adipogenesis were established. We investigated the role of 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 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 evidences that remarkable DNA hypermethylation and histone 3 and 4 hypoacetylation in -1286bp/-1065bp 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.
