Ding Yun, Gao Yu, Sun Jianjun, Cai Zhigang
Department of Cardiothoracic Surgery, Naval Medical Center, Naval Medical University (Second Military Medical University), Shanghai, 200052, People's Republic of China.
Department of Gastroenterology, Naval Medical Center, Naval Medical University (Second Military Medical University), Shanghai, 200052, People's Republic of China.
Int J Gen Med. 2025 Sep 1;18:5013-5031. doi: 10.2147/IJGM.S530523. eCollection 2025.
Impaired clinical fracture healing remains a major challenge, with surgical treatment often insufficient in patients with metabolic disorders or comorbidities such as diabetes and osteoporosis. Recent advances in metabolomics have brought the Sirtuin protein family to the forefront of bone regeneration research. These NAD⁺-dependent deacetylases exhibit cell-specific expression and regulate critical processes in osteoblasts and osteoclasts, linking glucose metabolism with bone remodeling. Sirtuins influence key pathways such as Wnt/β-catenin, AMPK, and mTOR, offering novel insights into the mechanisms of fracture healing. Emerging pharmacological strategies targeting Sirtuins show promising results in preclinical models. This review highlights the potential of Sirtuin-based interventions as therapeutic targets in the metabolic regulation of bone repair.
临床骨折愈合受损仍然是一个重大挑战,对于患有代谢紊乱或合并症(如糖尿病和骨质疏松症)的患者,手术治疗往往并不充分。代谢组学的最新进展使沉默调节蛋白(Sirtuin)家族成为骨再生研究的前沿领域。这些依赖烟酰胺腺嘌呤二核苷酸(NAD⁺)的脱乙酰酶表现出细胞特异性表达,并调节成骨细胞和破骨细胞中的关键过程,将葡萄糖代谢与骨重塑联系起来。沉默调节蛋白影响关键信号通路,如Wnt/β-连环蛋白、腺苷酸活化蛋白激酶(AMPK)和哺乳动物雷帕霉素靶蛋白(mTOR),为骨折愈合机制提供了新的见解。针对沉默调节蛋白的新兴药理学策略在临床前模型中显示出有希望的结果。本综述强调了基于沉默调节蛋白干预作为骨修复代谢调节治疗靶点的潜力。