衰老
成骨细胞
细胞生物学
糖皮质激素
线粒体
间充质干细胞
干细胞
化学
细胞分化
生物
内分泌学
基因
生物化学
体外
作者
Nianping Cao,Zhihang Wang,Chongjun Huang,Bobo Chen,Pengyu Zhao,Ying Xu,Ye Tian
标识
DOI:10.1016/j.archger.2023.105080
摘要
Mitochondrial dysfunction plays a crucial role in the development of glucocorticoid-induced osteoporosis (GIO). Cytidine monophosphate kinase 2 (Cmpk2), an essential mitochondria-associated gene, promotes the production of free mitochondrial DNA, which leads to the formation of inflammasome-mediated inflammatory factors. However, the specific role of Cmpk2 in GIO remains unclear. In this study, we report that glucocorticoids induce cellular senescence within the bone, particularly in bone marrow mesenchymal stem cells and preosteoblasts. We discovered that glucocorticoids cause mitochondrial dysfunction in preosteoblasts, increasing cellular senescence. Moreover, we observed elevated expression of Cmpk2 in preosteoblasts following glucocorticoid exposure. Inhibiting Cmpk2 expression alleviates glucocorticoid-induced cellular senescence and promotes osteogenic differentiation by improving mitochondrial function. Our study uncovers new mechanisms underlying glucocorticoid-induced senescence in stem cells and preosteoblasts, highlighting the potential of inhibiting the mitochondrial gene Cmpk2 to reduce senescence and enhance osteogenic differentiation. This finding offers a potential therapeutic approach for the treatment of GIO.
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