Modulation of SIRT6 activity acts as an emerging therapeutic implication for pathological disorders in the skeletal system
作者机构：Department of Biomedical Materials ScienceArmy Medical UniversityChongqing 400038China Department of OrthopedicsSouthwest HospitalArmy Medical UniversityChongqing 400038China
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2023年第10卷第3期
页 面：864-876页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 10[医学]
主 题：Intervertebral disc degeneration(IDD) Osteoarthritis(OA) Osteoporosis(OP) Rheumatoid arthritis(RA) SIRT6(SIR2-Like protein 6) SIRT6 activator
摘 要：The skeletal system is a dynamically balanced system, which undergoes continuous bone resorption and formation to maintain bone matrix homeostasis. As an important ADP-ribosylase and NAD+-dependent deacylase, SIRT6 (SIR2-like protein 6) is widely expressed on various kinds of bone cells, such as chondrocytes, osteoblasts, osteoclasts. The aberration of SIRT6 impairs gene expression (e.g., NF-κB and Wnt target genes) and cellular functions (e.g., DNA repair, glucose and lipid metabolism, telomeric maintenance), which disturbs the dynamic balance and ultimately leads to several bone-related diseases. In this review, we summarize the critical roles of SIRT6 in the onset and progression of bone-related diseases including osteoporosis, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, as well as the relevant signaling pathways. In addition, we discuss the advances in the development of SIRT6 activators and elucidate their pharmacological profiles, which may provide novel treatment strategies for these skeletal diseases.
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