FoxO1/NLRP3 Inflammasome Promotes Age-Related Alveolar Bone Resorption.

Abstract

Periodontitis is the utmost common chronic oral disease that exhibits intense susceptibility to aging. Aging is characterized by persistent sterile low-grade inflammation, leading to age-related periodontal complications represented by alveolar bone loss. Currently, forkhead transcription factor O1 (FoxO1) is generally believed to have a significant role in body development, senescence, cell viability, and oxidative stress in numerous organs and cells. However, the role of this transcription factor in mediating age-related alveolar bone resorption has not been examined. In this study, FoxO1 deficiency was discovered to have a beneficial correlation with halting the progression of alveolar bone resorption in aged mice. To further investigate the function of FoxO1 in age-related alveolar bone resorption, osteoblastic-specific FoxO1 knockout mice were generated, leading to an amelioration in alveolar bone loss compared to aged-matched wild-type mice, manifested as enhanced osteogenic potential. Mechanistically, we identified enhancement of the NLRP3 inflammasome signaling in FoxO1-deficient osteoblasts in the high dose of reactive oxygen species. Concordant with our study, MCC950, a specific inhibitor of NLRP3 inflammasome, greatly rescued osteoblast differentiation under oxidative stress. Our data shed light on the manifestations of FoxO1 depletion in osteoblasts and propose a possible mechanism for the therapy of age-related alveolar bone loss.

• Authors: Z Wang, F Zhou, X Feng, H Li, C Duan, Y Wu, Y Xiong
• Journal: Journal of dental research (J Dent Res) Vol. 102 Issue 8 Pg. 919-928 (07 2023) ISSN: 1544-0591 [Electronic] United States
• PMID: 37203197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Forkhead Box Protein O1

Topics

• Animals
• Mice
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Alveolar Bone Loss
• Forkhead Box Protein O1
• Bone and Bones
• Osteoblasts