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

J Periodontol. 2022 Dec;93(12):1961-1973. doi: 10.1002/JPER.21-0473. Epub 2022 Jan 27.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: apoptosis; cementum; gene regulation; orthodontics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Sirtuin 1
  • Resveratrol
  • Arginine
  • Sirt1 protein, mouse
  • Sirt1 protein, rat