Dynamic and distinct histone modifications of osteogenic genes during osteogenic differentiation
Dynamic and distinct histone modifications of osteogenic genes during osteogenic differentiation
复制标题
成骨分化过程中成骨基因的动态且独特的组蛋白修饰
DOI：
10.1093/jb/mvv059
复制
发表时间：
2015
影响因子：
2.7
通讯作者：
Zhao Qing-Hua
中科院分区：
文献类型：
--
作者：
Zhang Yong-Xing;Sun Hai-Lang;Liang He;Li Kai;Fan Qi-Ming;Zhao Qing-Hua
骨髓基质细胞（BMSCs）成骨缺陷是许多骨骼疾病的共同病理表型，组蛋白修饰在其中起着重要作用。然而，很少有研究探讨不同的组蛋白修饰在成骨过程中的动力学。在这项研究中，我们检查了H3 K9/K14和H4 K1/2乙酰化的动态; H3 K4单甲基化、双甲基化和三甲基化;成骨基因、侏儒相关转录因子2（Runx 2）、osterix（Osx）、碱性磷酸酶、骨唾液酸蛋白和H3 K27中的H3 K9二甲基化和H3 K27三甲基化在C3 H10 T1/2成骨过程中。在C3 H10 T1/2成骨过程中，成骨基因H3和H4乙酰化和H3 K4二甲基化水平升高，H3 K9二甲基化和H3 K27三甲基化水平降低。C3 H10 T1/2的成骨作用可通过改变H3和H4乙酰化以及H3 K27三甲基化的模式来调节。在糖皮质激素诱导的骨质疏松症小鼠模型中，我们观察到骨质疏松BMSCs的成骨潜能衰减与Runx 2和Osx基因中的H3和H4低乙酰化和H3 K27高三甲基化平行。当H3和H4乙酰化水平升高，H3 K27三甲基化水平降低时，可有效地挽救受损的骨髓间充质干细胞的成骨潜能。这些观察提供了对成骨分化的机制和骨质疏松症的病理生理学的更深入的了解，并可用于设计新的药物和开发新的治疗方法来治疗骨骼疾病。
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.