Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Eur J Cell Biol. 2023 Jun;102(2):151297. doi: 10.1016/j.ejcb.2023.151297. Epub 2023 Feb 10.
Microenvironment biophysical factors such as matrix stiffness can noticeably affect the differentiation of mesenchymal stem cells (MSCs). In this mechanobiology transduction process, mitochondria are shown to be an active participant. The present study aims to systematically elucidate the phenotypic and functional changes of mitochondria during the stiffness-mediated osteogenic differentiation. Additionally, the effect of mitochondria transfer on the osteogenesis of impaired MSCs caused by stiffness was investigated. Human periodontal ligament stem cells (PDLSCs) were used as model cells in the current study. Low stiffness restrained the cell spreading and significantly inhibited the proliferation and osteogenic differentiation of PDLSCs. Mitochondria of PDLSCs cultured on low stiffness exhibited shorter length, rounded shape, fusion/fission imbalance, ROS and mitophagy level increase, and ATP production reduction. The inhibited mitochondria function and osteogenic differentiation capacity were recovered to near-normal levels after transferring the mitochondria of PDLSCs cultured on the high stiffness. This study indicated that low matrix stiffness altered the mitochondrial morphology and induced systematical mitochondrial dysfunction during the osteogenic differentiation of MSCs. Mitochondria transfer was proved to be a feasible technique for maintaining MSCs function in vitro by reversing the osteogenesis ability.
微环境的生物物理因素，如基质硬度，可以显著影响间充质干细胞（MSCs）的分化。在这个力学生物学转导过程中，线粒体被证明是一个活跃的参与者。本研究旨在系统阐明线粒体在刚度介导的成骨分化过程中的表型和功能变化。此外，还研究了线粒体转移对刚度引起的受损 MSC 成骨的影响。本研究以人牙周膜干细胞（PDLSCs）为模型细胞。低硬度限制了细胞的铺展，并显著抑制了 PDLSCs 的增殖和成骨分化。在低刚度下培养的 PDLSCs 的线粒体长度较短，形状呈圆形，融合/裂变失衡，ROS 和线粒体自噬水平增加，ATP 生成减少。将高刚度培养的 PDLSCs 的线粒体转移后，抑制的线粒体功能和成骨分化能力恢复到接近正常水平。本研究表明，低基质硬度在 MSC 的成骨分化过程中改变了线粒体的形态，并诱导了系统的线粒体功能障碍。线粒体转移通过逆转成骨能力被证明是一种维持 MSC 体外功能的可行技术。
