Z Wang, F Zhou, X Feng, H Li, C Duan, Y Wu, Y Xiong
{"title":"fox01 /NLRP3炎性体促进年龄相关性牙槽骨吸收。","authors":"Z Wang, F Zhou, X Feng, H Li, C Duan, Y Wu, Y Xiong","doi":"10.1177/00220345231164104","DOIUrl":null,"url":null,"abstract":"<p><p>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, <i>FoxO1</i> 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 <i>FoxO1</i> 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 <i>FoxO1</i>-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 <i>FoxO1</i> depletion in osteoblasts and propose a possible mechanism for the therapy of age-related alveolar bone loss.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 8","pages":"919-928"},"PeriodicalIF":5.7000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"FoxO1/NLRP3 Inflammasome Promotes Age-Related Alveolar Bone Resorption.\",\"authors\":\"Z Wang, F Zhou, X Feng, H Li, C Duan, Y Wu, Y Xiong\",\"doi\":\"10.1177/00220345231164104\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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, <i>FoxO1</i> 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 <i>FoxO1</i> 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 <i>FoxO1</i>-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 <i>FoxO1</i> depletion in osteoblasts and propose a possible mechanism for the therapy of age-related alveolar bone loss.</p>\",\"PeriodicalId\":15596,\"journal\":{\"name\":\"Journal of Dental Research\",\"volume\":\"102 8\",\"pages\":\"919-928\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Dental Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/00220345231164104\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Dental Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/00220345231164104","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
FoxO1/NLRP3 Inflammasome Promotes Age-Related Alveolar Bone Resorption.
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.
期刊介绍:
The Journal of Dental Research (JDR) is a peer-reviewed scientific journal committed to sharing new knowledge and information on all sciences related to dentistry and the oral cavity, covering health and disease. With monthly publications, JDR ensures timely communication of the latest research to the oral and dental community.