Mechanical force induces mitophagy-mediated anaerobic oxidation in periodontal ligament stem cells

作者：Zijie Zhang, Shuyue Cui, Yajing Fu, Jixiao Wang, Jiani Liu, Fulan Wei · 发表于：Cellular & Molecular Biology Letters · 年份：2023 · DOI：10.1186/s11658-023-00453-w · 被引用次数：31 · 研究领域：Autophagy in Disease and Therapy、Bone Metabolism and Diseases、Oral microbiology and periodontitis research

BACKGROUND: The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can play a decisive role in regulating critical metabolic enzymes and pathways of stem cells. Periodontal ligament stem cells (PDLSCs) are momentous effector cells that transform mechanical force into biological signals during the reconstruction of alveolar bone. However, mechanical stimuli-induced alteration of oxidative characteristics in PDLSCs and the underlying mechanisms have not been fully elucidated. METHODS: Herein, we examined the expression of LDH and COX4 by qRT-PCR, western blot, immunohistochemistry and immunofluorescence. We detected metabolites of lactic acid and reactive oxygen species for functional tests. We used tetramethylrhodamine methyl ester (TMRM) staining and a transmission electron microscope to clarify the mitochondrial status. After using western blot and immunofluorescence to clarify the change of DRP1, we further examined MFF, PINK1, and PARKIN by western blot. We used cyclosporin A (CsA) to confirm the regulation of mitophagy and ceased the stretching as a rescue experiment. RESULTS: Herein, we ascertained that mechanical force could increase the level of LDH and decrease the expression of COX4 in PDLSCs. Simultaneously, the yield of reactive oxygen species (ROS) in PDLSC reduced after stretching, while lactate acid augmented significantly. Furthermore, mitochondrial fun...