Parkin Acetylation-Mediated Mitophagy Orchestrates Periodontal Ligament Stem Cell Osteogenesis and Bone Regeneration...

To investigate the functional significance of mitophagy in age-related osteogenic decline and the underlying mechanisms using in vivo and in vitro models.

An alveolar bone defect model in aged mice and a serial passaging-induced ageing model of human periodontal ligament stem cells (PDLSCs) were established. Osteogenic potential in mice was assessed by micro-CT, immunofluorescence, immunohistochemical analyses and histological staining. Osteogenic differentiation, mitochondrial function and mitophagy in PDLSCs were assessed using molecular techniques, cytochemical assays and imaging approaches. HDAC2-Parkin interactions and Parkin acetylation status were examined by mass spectrometry and immunoprecipitation to uncover key mechanisms.

Senescent PDLSCs exhibited impaired mitophagy and osteogenic capacity. Enhancing mitophagy restored osteogenesis of senescent PDLSCs and bone regeneration in aged mice. Mechanistically, HDAC2-mediated deacetylation of Parkin suppressed mitophagy and osteogenesis during ageing.

Activation of mitophagy reverses age-associated declines in osteogenic function, highlighting mitophagy as a therapeutic target for enhancing bone repair in the ageing population.