Effect of Mitophagy on the Tension-Driven Osteogenic Differentiation of Periodontal Ligament Stem Cells During Ageing.

OBJECTIVES: Age-related differences in orthodontic tooth movement (OTM) and mechanical force-induced osteogenesis have been reported. Mitophagy plays a crucial role in bone metabolism and various age-related diseases, and BCL2-interacting protein 3 (BNIP3) is a mitophagy-related receptor. This study aimed to elucidate the role of mitophagy associated with BNIP3 on age-related changes in the orthodontic tension-driven osteogenic differentiation of periodontal ligament stem cells. MATERIALS AND METHODS: Periodontal ligament stem cells (PDLSCs) from adolescent (6-week-old) and adult (8-month-old) rats were cultured and stretched using a Flexcell system. The effects of mitophagy associated with BNIP3 were assessed via real-time quantitative PCR and western blot analyses. Moreover, a rat model of OTM across different ages was established for in vivo analyses. The function of mitophagy in age-related osteogenic differentiation induced by orthodontic force on the tension side was evaluated via microcomputed tomography and immunohistochemistry analyses. RESULTS: Under tension, the expression of the mitophagy factor BNIP3, the autophagy factor microtubule-associated protein light chain 3 (LC3), and the osteogenic factors Runt-related transcription factor 2 (RUNX2) and Osterix (OSX) significantly increased in rPDLSCs over time. The expression of these factors was also upregulated in the rat OTM model under orthodontic force. Compared with the adolescent group, the adult group exhibited lower levels of mitophagy and osteogenic differentiation after tension both in vivo and in vitro. Enhanced mitophagy induced by carbonyl cyanide m-chlorophenyl hydrazone upregulated the expression of the aforementioned factors in an adult rat OTM model. CONCLUSIONS: Mitophagy is associated with osteogenic activity induced by tension force in PDLSCs and may play a substantial role in regulating age-related changes in the OTM process.