Upregulation of mitochondrial dynamics is responsible for osteogenic differentiation of mesenchymal stem cells cultured on self-mineralized collagen membranes.
Upregulation of mitochondrial dynamics is responsible for osteogenic differentiation of mesenchymal stem cells cultured on self-mineralized collagen membranes.
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DOI：
10.1016/j.actbio.2021.09.039
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发表时间：
2021-09
影响因子：
9.7
通讯作者：
Mei‐chen Wan;Xiaoyan Tang;Jing Li;Peng-Lai Gao;Fu Wang;Minjuan Shen;Jun‐ting Gu;F. Tay;
中科院分区：
文献类型：
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作者：
Mei‐chen Wan;Xiaoyan Tang;Jing Li;Peng-Lai Gao;Fu Wang;Minjuan Shen;Jun‐ting Gu;F. Tay;
用高分子量聚丙烯酸（HPAA）交联的胶原膜能够通过原位纤维内矿化而自我矿化。这些HPAA交联的胶原膜（HCM）已被证明可以促进间充质干细胞（MSC）的成骨分化，并增强体内骨再生。然而，这些过程中涉及的生物触发因素和相关机制尚不清楚。在这里，我们确定了HCM介导的骨髓间充质干细胞成骨分化的线粒体动力学的贡献。当MSC在HCM上培养时，线粒体发生标记物显著上调，使MSC向成骨分化。线粒体融合形成相互连接的线粒体网络，以响应高能量需求。骨髓间充质干细胞中的线粒体分裂也由HCM触发;分裂在14天时略微下降以恢复线粒体动力学的平衡。线粒体自噬是另一个调节线粒体动力学的事件，它的发生是为了清除功能失调的线粒体，并将受损的线粒体与网络的其余部分隔离开来。骨髓间充质干细胞在HCM存在下的线粒体吞噬水平显著升高。综上所述，本研究结果表明，线粒体动力学的上调，通过成骨，融合，分裂和线粒体自噬是负责HCM介导的成骨分化的MSCs。声明的重要性高分子量聚丙烯酸（HPAA）交联胶原膜（HCM）被发现，促进原位骨再生，因为它可以刺激间充质干细胞（MSCs）的成骨分化。然而，这些过程中涉及的生物触发因素和相关机制尚不清楚。本研究确定，激活线粒体动力学是中央参与HCM介导的骨髓间充质干细胞的成骨分化。HCM加速骨形成并调节线粒体网络的稳态，以响应成骨分化增加的能量需求。同时，线粒体自噬活跃地发生，以从线粒体网络的其余部分中去除功能障碍的线粒体。线粒体自噬参与骨髓间充质干细胞的成骨分化的鉴定为仿生矿化在骨组织再生中的应用开辟了新的前景。
Collagen membranes crosslinked with high molecular weight polyacrylic acid (HPAA) are capable of self-mineralization viain situintrafibrillar mineralization. These HPAA-crosslinked collagen membranes (HCM) have been shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs) and enhance bone regenerationin vivo. Nevertheless, the biological triggers involved in those processes and the associated mechanisms are not known. Here, we identified the contribution of mitochondrial dynamics in HCM-mediated osteogenic differentiation of MSCs. Mitochondriogenesis markers were significantly upregulated when MSCs were cultured on HCM, committing the MSCs to osteogenic differentiation. The mitochondria fused to form an interconnected mitochondrial network in response to the high energy requirements. Mitochondrial fission in MSCs was also triggered by HCM; fission slightly declined at 14 days to restore the equilibrium in mitochondrial dynamics. Mitophagy, another event that regulates mitochondrial dynamics, occurred actively to remove dysfunctioned mitochondria and isolate damaged mitochondria from the rest of network. The mitophagy level of MSCs was significantly elevated in the presence of HCM. Taken together, the present findings indicate that upregulation of mitochondrial dynamics via mitochondriogenesis, fusion, fission and mitophagy is responsible for HCM-mediated osteogenic differentiation of MSCs.Statement of significanceHigh molecular weight polyacrylic acid (HPAA)-crosslinked collagen membrane (HCM) was found to promotein-situbone regeneration because of it can stimulate osteogenic differentiation of mesenchymal stem cells (MSCs). Nevertheless, the biological triggers involved in those processes and associated mechanisms are not known. This study identifies that activation of mitochondrial dynamics is centrally involved in HCM-mediated osteogenic differentiation of MSCs. The HCM accelerates mitochondriogenesis and regulates homeostasis of the mitochondrial network in response to the increased energy demand for osteogenic differentiation. Concomitantly, mitophagy actively occurs to remove dysfunctioned mitochondria from the rest of the mitochondrial network. Identification of the involvement of mitophagy in HCM-mediated osteogenic differentiation of MSCs opens new vistas in the application of biomimetic mineralization in bone tissue regeneration.