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Mitophagy plays a crucial role in bone metabolism and various age\u2010related diseases. However, the impact of mitophagy on the bone remodeling process during OTM remains elusive. Using adolescent (6\u2009weeks old) and adult (12\u2009months old) rats, we established OTM models and observed that orthodontic force increased the expression of the mitophagy proteins PTEN\u2010induced putative kinase 1 (PINK1) and Parkin, as well as the number of tartrate\u2010resistant acid phosphatase\u2010positive osteoclasts and osteocalcin\u2010positive osteoblasts. These biological changes were found to be age\u2010related. In\u00a0vitro, compression force loading promoted PINK1\/Parkin\u2010dependent mitophagy in periodontal ligament stem cells (PDLSCs) derived from adolescents (12\u201316\u2009years old) and adults (25\u201335\u2009years old). Furthermore, adult PDLSCs exhibited lower levels of mitophagy, impaired mitochondrial function, and a decreased ratio of RANKL\/OPG compared to young PDLSCs after compression. Transfection of siRNA confirmed that inhibition of mitophagy in PDLSC resulted in decreased mitochondrial function and reduced RANKL\/OPG ratio. Application of mitophagy inducer Urolithin A enhanced bone remodeling and accelerated OTM in rats, while the mitophagy inhibitor Mdivi\u20101 had the opposite effect. These findings indicate that force\u2010stimulated PDLSC mitophagy contributes to alveolar bone remodeling during OTM, and age\u2010related impairment of mitophagy negatively impacts the PDLSC response to mechanical stimulus. Our findings enhance the understanding of mitochondrial mechanotransduction and offer new targets to tackle current clinical challenges in orthodontic therapy.<\/jats:p>","DOI":"10.1096\/fj.202401280r","type":"journal-article","created":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T05:19:55Z","timestamp":1722662395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Age\u2010related mitophagy regulates orthodontic tooth movement by affecting PDLSCs mitochondrial function and RANKL\/OPG"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-5692","authenticated-orcid":false,"given":"Tong","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology Sun Yat\u2010Sen University  Guangzhou Guangdong 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