表观遗传和代谢调控间充质干细胞成骨分化的研究进展

间充质干细胞是目前硬组织再生与修复中最为重要的种子细胞,在临床应用中前景广阔,因此其命运调控以及定向分化机制一直是领域内的重点研究方向。但由于间充质干细胞的异质性以及对其定向分化调控机制尚未完全清楚等诸多原因,制约了间充质干细胞在临床治疗中的应用。近些年来越来越多的研究证明,在间充质干细胞成骨分化过程中表观遗传修饰发挥了重要调控作用;表观遗传调控异常与骨质疏松症的发生有关,且干预表观遗传修饰的小分子化合物具有改善骨质疏松的潜能。另一方面,营养物质代谢,尤其是葡萄糖代谢 (糖代谢) 不仅为细胞生理活动提供必需的能量物质, 其代谢中间产物也是干细胞增殖、分化的调控因子;表观遗传修饰与糖代谢紧密关联,对间充质干细胞的生物学特性、命运决定起到至关重要的作用。在本文中,我们简要叙述了糖代谢和表观遗传修饰调控间充质干细胞成骨分化的研究进展和表观遗传在骨质疏松症中的临床应用前景。

Research progress on the epigenetic and metabolic regulation on osteogenesis of MSCs

Until now, mesenchymal stem cells (MSCs) are the most important candidates for calcified tissue regeneration and injury repair, showing broad clinical application prospects. Therefore, the mechanism of fate determination and differentiation regulation has been the fundamental question in the field. However, due to many reasons, such as the heterogeneity and limited knowledge of regulatory mechanisms, the further investigation and clinical application of MSCs are restricted. In recent years, emerging studies have proved that epigenetic modification plays an important regulatory role in the process of osteogenic differentiation of MSCs. Abnormal epigenetic regulation is associated with the development of osteoporosis, and small molecules that interfere with epigenetic modifications have the potential to improve osteoporosis. On the other hand, nutrient metabolism, especially glucose metabolism, is a necessary energy source for cell physiological activities and a regulatory factor for stem cell proliferation and differentiation. They are closely related and play a crucial role in the biological characteristics and fate determination of MSCs. In this paper, we briefly describe the research progress of glucose metabolism and epigenetic modifications in regulating osteogenic differentiation of MSCs and the prospect of clinical application of epigenetics in osteoporosis.