Knockdown of SIRT3 perturbs protective effects of irisin against bone loss in diabetes and periodontitis

作者全名："Li, Guangyue; Qin, Han; Zhou, Mengjiao; Zhang, Tingwei; Zhang, Yang; Ding, Huifen; Xu, Ling; Song, Jinlin"

作者地址："[Li, Guangyue; Qin, Han; Zhou, Mengjiao; Zhang, Tingwei; Zhang, Yang; Ding, Huifen; Xu, Ling; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Li, Guangyue; Qin, Han; Zhou, Mengjiao; Zhang, Tingwei; Zhang, Yang; Ding, Huifen; Xu, Ling; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Li, Guangyue; Qin, Han; Zhou, Mengjiao; Zhang, Tingwei; Zhang, Yang; Ding, Huifen; Xu, Ling; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China"

通信作者："Song, JL (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China."

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000956541600001

JCR分区：Q1

影响因子：7.1

年份：2023

卷号：200

期号：　

开始页：11

结束页：25

文献类型：Article

关键词：Periodontitis; Irisin; Sirtuin 3; Oxidative stress; Mitochondria; Alveolar bone homeostasis

摘要："A well-recognized risk factor for periodontitis, diabetes mellitus (DM) aggravates periodontal disease with increasing alveolar bone loss. As a novel myokine, irisin is closely linked with bone metabolism. Nonetheless, the effects of irisin on periodontitis under diabetic conditions and the underlying mechanisms remain poorly understood. Here, we showed that local irisin treatment ameliorates alveolar bone loss and oxidative stress, increases SIRT3 expression within periodontal tissues of our experimentally-induced diabetes and periodontitis (DP) rat models. By culturing the periodontal ligament cells (PDLCs) in vitro, we found that irisin could partially rescue inhibited cell viability, mitigate accumulated intracellular oxidative stress, ameliorate mitochondrial dysfunctions, and restore disturbed osteogenic and osteoclastogenic capacities of PDLCs when exposed to high glucose and pro-inflammatory stimulation. Furthermore, lentivirus-mediated SIRT3 knockdown was employed to unravel the underlying mechanism by which SIRT3 mediated irisin's beneficial effects on PDLCs. Meanwhile, in SIRT3-deficient mice, irisin treatment did not protect against alveolar bone destruction and oxidative stress accumulation in DP models, which underlined the crucial role of SIRT3 in mediating the positive effects of irisin on DP. Our findings, for the first time, revealed that irisin attenuates alveolar bone loss and oxidative stress via activation of the SIRT3 signaling cascade, and highlighted its therapeutic potential for the treatment of DP."

基金机构："National Natural Science Foundation of China [81800938, 31971282]; Natural Science Foundation of Chongqing, China [CSTB2022NSCQ- MSX1021]; Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2023MSXM087]"

基金资助正文："We are grateful to Professor Gangyi Yang from the Second Affiliated Hospital of Chongqing Medical University, for his kind donation of SIRT3-/-mice with C57BL/6 backgrounds. This work was supported by the National Natural Science Foundation of China (Grant No. 81800938 and 31971282). This research was also sponsored by Natural Science Foundation of Chongqing, China (Grant No. CSTB2022NSCQ-MSX1021) and Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (Project No. 2023MSXM087)."