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作 者:Zicai Dong Chuan Yang Jiulin Tan Ce Dou Yueqi Chen
机构地区:[1]Department of Biomedical Materials Science,Army Medical University,Chongqing 400038,China [2]Department of Orthopedics,Southwest Hospital,Army Medical University,Chongqing 400038,China
出 处:《Genes & Diseases》2023年第3期864-876,共13页基因与疾病(英文)
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.
关 键 词:Intervertebral disc degeneration(IDD) Osteoarthritis(OA) Osteoporosis(OP) Rheumatoid arthritis(RA) SIRT6(SIR2-Like protein 6) SIRT6 activator
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