General Practice Ward/International Medical Center Ward, General Practice Medical Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Stem Cell Res Ther. 2023 Jun 25;14(1):166. doi: 10.1186/s13287-023-03393-6.
Age-associated bone diseases such as osteoporosis (OP) are common in the elderly due to skeletal ageing. The process of skeletal ageing can be accelerated by reduced proliferation and osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs). Senescence of BM-MSCs is a main driver of age-associated bone diseases, and the fate of BM-MSCs is tightly regulated by histone modifications, such as methylation and acetylation. Dysregulation of histone modifications in BM-MSCs may activate the genes related to the pathogenesis of skeletal ageing and age-associated bone diseases. Here we summarize the histone methylation and acetylation marks and their regulatory enzymes that affect BM-MSC self-renewal, differentiation and senescence. This review not only describes the critical roles of histone marks in modulating BM-MSC functions, but also underlines the potential of epigenetic enzymes as targets for treating age-associated bone diseases. In the future, more effective therapeutic approaches based on these epigenetic targets will be developed and will benefit elderly individuals with bone diseases, such as OP.
与年龄相关的骨骼疾病，如骨质疏松症（OP），在老年人中很常见，这是由于骨骼老化所致。骨髓间充质干细胞（BM-MSCs）增殖和成骨能力的降低会加速骨骼老化过程。BM-MSCs 的衰老是与年龄相关的骨骼疾病的主要驱动因素，BM-MSCs 的命运受到组蛋白修饰（如甲基化和乙酰化）的严格调控。BM-MSCs 中组蛋白修饰的失调可能会激活与骨骼老化和与年龄相关的骨骼疾病发病机制相关的基因。在这里，我们总结了影响 BM-MSC 自我更新、分化和衰老的组蛋白甲基化和乙酰化标记及其调节酶。本综述不仅描述了组蛋白标记在调节 BM-MSC 功能方面的关键作用，还强调了表观遗传酶作为治疗与年龄相关的骨骼疾病的靶点的潜力。未来，将开发基于这些表观遗传靶点的更有效的治疗方法，使患有骨骼疾病（如 OP）的老年人受益。
