近期，《细胞与分子医学杂志》（Journal of Cellular and Molecular Medicine）在线发表了中科院健康所戴尅戎院士组关于骨髓间充质干细胞成骨与成脂分化平衡调控机制方面的研究进展。
在人类许多疾病中可以见到骨组织与脂肪组织“此消彼长”的现象。例如，在衰老、长期制动和大量使用皮质激素等情况下，骨形成的减少总是与骨髓中脂肪组织的增加相伴发生；患有进行性骨异生的病人在其脂肪组织内常发生异位骨化。由于成骨细胞和脂肪细胞共同来源于骨髓间充质干细胞，因此上述情况提示人们骨髓间充质干细胞成骨分化与成脂分化不是彼此孤立的过程，而是存在着相互制约的平衡关系。目前该领域已成为干细胞生物学研究的热点。在本研究中，范启明等研究人员着眼于骨髓间充质干细胞成骨与成脂分化平衡，选择C/EBPα为靶基因，研究它在BMP-2诱导的C3H10T1/2细胞向成骨细胞定向分化和成骨-成脂转分化过程中的基因表达模式、基因表达调控机制和它对C3H10T1/2细胞成骨分化的调节作用。结果显示，BMP-2诱导C3H10T1/2细胞向成骨细胞定向分化过程中C/EBPα表达量先上调后下调；过表达C/EBPα可以抑制BMP-2诱导的C3H10T1/2细胞的成骨分化；与早期相比，BMP-2诱导C3H10T1/2细胞向成骨细胞分化的末期细胞成脂分化潜能减弱，它是由于C/EBPα对成脂信号的可诱导性减弱造成的；与早期相比，BMP-2诱导C3H10T1/2细胞向成骨细胞分化的末期C/EBPα基因转录起始位点上游-1286bp/-1065bp区域呈现显著的DNA高甲基化和组蛋白H3、H4的去乙酰化；-1286bp/-1065bp区域的高甲基化不仅导致C/EBPα mRNA表达量下调，而且能使C/EBPα对成脂信号的可诱导性减弱。此项研究可以为积极预防和有效治疗以骨形成减少和脂肪异常增生为症状的疾病提供理论基础。
此项研究得到973计划（2007CB936101）、国家自然科学基金（30700402 & 30871435）和上海市启明星计划（07QA14062）的资金资助。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Cellular and Molecular Medicine 16 Dec 2008DOI:10.1111/j.1582-4934.2008.00606.x
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.
