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

• Published in: Free radical biology & medicine Vol. 200; pp. 11 - 25
• Main Authors: Li, Guangyue, Qin, Han, Zhou, Mengjiao, Zhang, Tingwei, Zhang, Yang, Ding, Huifen, Xu, Ling, Song, Jinlin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2023
• Subjects: Alveolar bone homeostasis; Alveolar Bone Loss - drug therapy; Alveolar Bone Loss - prevention & control; Animals; Diabetes Mellitus; Fibronectins - genetics; Irisin; Mice; Mitochondria; Oxidative Stress; Periodontitis; Periodontitis - drug therapy; Periodontitis - genetics; Rats; Sirtuin 3; Sirtuin 3 - genetics; Irisin; Oxidative stress; Mitochondria; Sirtuin 3; Periodontitis; Alveolar bone homeostasis
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.02.023

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. [Display omitted] •Irisin attenuates alveolar bone destruction in diabetes and periodontitis.•SIRT3-KO abolishes the effect of irisin on oxidative stress and alveolar bone loss.•Irisin ameliorates oxidative stress and mitochondrial dysfunction via SIRT3 in PDLCs.•SIRT3 silencing diminishes the modulatory impacts of irisin on PDLCs.