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。
中科院健康所，上海交通大学医学院戴尅戎院士等在J Cell Mol Med杂志上发表了骨髓间充质干细胞成骨与成脂分化平衡调控机制方面的新成果，这一研究成果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。在这篇文章中，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。
戴尅戎院士研究组还与中科院上海硅酸盐研究所常江教授合作，通过体外采用材料粉末抽提液培养骨髓间充质干细胞，发现在一定浓度下，镁黄长石粉末抽提液较同样浓度的β-三羟基磷灰石粉末抽提液，对骨髓间充质干细胞的增殖和其向成骨细胞的分化能力均有较大的提高。同时，体内兔股骨缺损修复实验同样也显示，镁黄长石支架材料较相同大小的β-三羟基磷灰石支架材料而言，具有更好的生物相容性和生物降解性。（生物谷Bioon.com）
2010年4月15日-16日，中科院上海生命科学院将联合国内众多干细胞专家于“2010年干细胞技术与应用讲座”发表演讲，详情见：http://www.stemcellasia.net/
生物谷推荐原始出处：
Journal of Cellular and Molecular Medicine Volume 13, Issue 8, Date: August 2009, Pages: 2489-2505
The role of CCAAT/enhancer binding protein (C/EBP)-α 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, Shanghai, People's Republic of China b Department of Orthopaedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
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)-α 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-α 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-α 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-α were involved in both of down-regulations. Our data suggest that C/EBP-α functions as regulator in the balance between osteogenesis and adipogenesis of C3H10T1/2 cells and may be a therapeutic target.
