L-arginine protects cementoblasts against hypoxia-induced apoptosis through Sirt1-enhanced autophagy

• Published in: Journal of periodontology (1970) Vol. 93; no. 12; p. 1961
• Main Authors: Xu, Lei, Tan, Xi, Bai, Siyu, Wu, Hongyan, Luo, Hong, Ye, Yusi, Fang, Lingli, Dai, Hongwei, Huang, Lan
• Format: Journal Article
• Language: English
• Published: United States 01.12.2022
• Subjects: Animals; Apoptosis; Arginine - pharmacology; Arginine - therapeutic use; Autophagy; Dental Cementum - metabolism; Hypoxia; Mice; Rats; Resveratrol - pharmacology; Resveratrol - therapeutic use; Root Resorption; Sirtuin 1 - metabolism; Sirtuin 1 - pharmacology; apoptosis; orthodontics; cementum; gene regulation
• DOI: 10.1002/JPER.21-0473

L-arginine (L-arg) can reduce apoptosis in a variety of cells. Cementoblast apoptosis is related to root resorption during orthodontic treatment. In the present study, we aimed to study the regulatory effect and potential mechanism of L-arg on cementoblast apoptosis and root resorption. The apoptosis-related mRNA and protein expression of murine cementoblast (OCCM-30) was assessed after L-arg treatment. To investigate the role of Sirtuin 1 (Sirt1) and autophagy in L-arg resistance to cementoblast apoptosis and root absorption, resveratrol, and EX527 were used to activate or inhibit Sirt1, and chloroquine (CQ) was used to inhibit autophagy. In vitro, L-arg inhibited hypoxia-induced apoptosis in OCCM-30. Further, L-arg increased Sirt1 expression whereas Sirt1 suppression by EX527 reversed the inhibitory effect of L-arg on cell apoptosis. Sirt1 activator resveratrol increased the ratio of microtubule-associated protein light chain 3 (LC3) II/I and decreased the expression of SQSTM1/p62 (p62), suggesting autophagy activation. Autophagy enhancement could reduce apoptosis. Caspase-3 and Bax expression was decreased, and Bcl-2 expression was increased. When autophagy was inhibited by CQ, the positive effects of Sirt1 were attenuated. In vivo, L-arg application reduced root resorption in rats, as demonstrated by decreased root absorption volume. Similarly, L-arg upregulated Sirt1, which activated autophagy in the root resorption model, and less root resorption was observed in the Sirt1 activation group. L-arg reduced cementoblast apoptosis in hypoxia and reduced root resorption induced by loading force in rats, which may be partly mediated by Sirt1-enhanced autophagy.