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

IF 6.8 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Clinical Periodontology Pub Date : 2025-09-07 DOI:10.1111/jcpe.70031

Kehan Zhang,Xiangyao Wang,Yuxiao Zhang,Yuanyuan Li,Yaxin Wu,Gaoshaer Nuerlan,Qilin Li,Jing Mao,Shiqiang Gong,Yan Liu

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Abstract

AIM To investigate the functional significance of mitophagy in age-related osteogenic decline and the underlying mechanisms using in vivo and in vitro models. MATERIALS AND METHODS 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. RESULTS 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. CONCLUSION Activation of mitophagy reverses age-associated declines in osteogenic function, highlighting mitophagy as a therapeutic target for enhancing bone repair in the ageing population.

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衰老过程中，帕金乙酰化介导的线粒体自噬调控牙周韧带干细胞成骨和骨再生。

目的通过体内和体外模型探讨线粒体自噬在年龄相关性成骨衰退中的功能意义及其机制。材料与方法建立老年小鼠牙槽骨缺损模型和人牙周韧带干细胞系列传代衰老模型。采用显微ct、免疫荧光、免疫组织化学和组织学染色等方法评价小鼠成骨潜能。使用分子技术、细胞化学分析和成像方法评估PDLSCs的成骨分化、线粒体功能和线粒体自噬。通过质谱和免疫沉淀检测HDAC2-Parkin相互作用和Parkin乙酰化状态，以揭示关键机制。结果衰老的PDLSCs表现出线粒体自噬和成骨能力受损。增强线粒体自噬可恢复衰老小鼠PDLSCs的成骨和骨再生。在机制上，hdac2介导的Parkin去乙酰化抑制了衰老过程中的线粒体自噬和成骨。结论：线粒体自噬的激活逆转了与年龄相关的成骨功能下降，突出了线粒体自噬作为增强老龄人群骨修复的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Periodontology 医学-牙科与口腔外科

CiteScore

13.30

自引率

10.40%

发文量

175

审稿时长

3-8 weeks

期刊介绍： Journal of Clinical Periodontology was founded by the British, Dutch, French, German, Scandinavian, and Swiss Societies of Periodontology. The aim of the Journal of Clinical Periodontology is to provide the platform for exchange of scientific and clinical progress in the field of Periodontology and allied disciplines, and to do so at the highest possible level. The Journal also aims to facilitate the application of new scientific knowledge to the daily practice of the concerned disciplines and addresses both practicing clinicians and academics. The Journal is the official publication of the European Federation of Periodontology but wishes to retain its international scope. The Journal publishes original contributions of high scientific merit in the fields of periodontology and implant dentistry. Its scope encompasses the physiology and pathology of the periodontium, the tissue integration of dental implants, the biology and the modulation of periodontal and alveolar bone healing and regeneration, diagnosis, epidemiology, prevention and therapy of periodontal disease, the clinical aspects of tooth replacement with dental implants, and the comprehensive rehabilitation of the periodontal patient. Review articles by experts on new developments in basic and applied periodontal science and associated dental disciplines, advances in periodontal or implant techniques and procedures, and case reports which illustrate important new information are also welcome.