State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, China; Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME 04074, USA.
Life Sci. 2021 Mar 15;269:119041. doi: 10.1016/j.lfs.2021.119041. Epub 2021 Jan 13.
Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, epigenetically regulates various cell metabolisms, including inflammation, tumorigenesis, and bone metabolism. Many clinical studies have found the potential of SIRT1 in predicting and treating bone-related disorders, such as osteoporosis and osteonecrosis, suggesting that SIRT1 might be a regulator of bone homeostasis. In order to identify the mechanisms that underlie the pivotal role of SIRT1 in bone homeostasis, many studies revealed that SIRT1 could maintain the balance between bone formation and absorption via regulating the ratio of osteoblasts to osteoclasts. SIRT1 controls the differentiation of mesenchymal stem cells (MSCs) and bone marrow-derived macrophages, increasing osteogenesis and reducing osteoclastogenesis. Besides, SIRT1 can enhance bone-forming cells' viability, including MSCs and osteoblasts under adverse conditions by resisting senescence, suppressing apoptosis, and promoting autophagy in favor of osteogenesis. Furthermore, the effect on bone vasculature homeostasis enables SIRT1 to become a valuable strategy for ischemic osteonecrosis and senile osteoporosis. The review systemically discusses SIRT1 pathways and the critical role in bone homeostasis and assesses whether SIRT1 is a potential target for manipulation and therapy, to lay a solid foundation for further researches in the future.
Sirtuin 1（SIRT1）是一种烟酰胺腺嘌呤二核苷酸依赖性去乙酰化酶，它在表观遗传水平上调节多种细胞代谢，包括炎症、肿瘤发生和骨代谢。许多临床研究发现 SIRT1 具有预测和治疗与骨骼相关疾病（如骨质疏松症和骨坏死）的潜力，这表明 SIRT1 可能是骨骼内稳态的调节剂。为了确定 SIRT1 在骨骼内稳态中发挥关键作用的机制，许多研究表明，SIRT1 可以通过调节成骨细胞与破骨细胞的比例来维持骨形成和吸收之间的平衡。SIRT1 控制间充质干细胞（MSCs）和骨髓来源巨噬细胞的分化，增加成骨作用，减少破骨细胞生成。此外，SIRT1 可以增强成骨细胞的活力，包括在不利条件下的 MSCs 和成骨细胞，通过抵抗衰老、抑制细胞凋亡和促进自噬来促进成骨作用。此外，对骨骼脉管系统稳态的影响使 SIRT1 成为缺血性骨坏死和老年性骨质疏松症的一种有价值的治疗策略。本综述系统地讨论了 SIRT1 途径及其在骨骼内稳态中的关键作用，并评估了 SIRT1 是否是一种潜在的操纵和治疗靶点，为未来的进一步研究奠定了基础。
