Zuo Jiyuan, Guo Qining, Fan Youzhun, Fu Xiaobin, Zhang Fengyuan, Zhu Xiaojing, Ning Chengyun, Kong Yuanyuan, Yu Peng, Zheng Jianmao
Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, China.
School of Materials Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510641, China.
Mater Today Bio. 2025 Jul 3;33:102050. doi: 10.1016/j.mtbio.2025.102050. eCollection 2025 Aug.
Inflammatory bone resorption is present in common oral and maxillofacial diseases. Macrophages play a crucial role in the inflammatory process of bone. It has been shown that M1 macrophages cause bone homeostasis and bone resorption disorders, and M2 macrophage-related cytokines inhibit osteoclast generation. To inhibit inflammatory bone resorption, a method that promotes M2 polarization and inhibits M1 polarization and osteoclastogenesis should be found. Studies have found that the mitochondrial membrane potential of macrophage increases during M2 differentiation, but decreases during M1 differentiation and osteoclast differentiation. Therefore, we hypothesized that it might be possible to use electric fields to regulate macrophage polarization and osteoclast differentiation. Piezoelectric materials have been shown to be a safe and effective material that can form piezoelectric potentials, but the role of piezoelectric nanomaterials and nano-electric fields in macrophage M2 differentiation and osteoclastogenesis remains to be investigated. Thus, in this study, polarized piezoelectric nanomaterial BaTiO (pBTO) is applied to macrophage cells to provide wireless intracellular electric field. Wireless intracellular electric field from pBTO is proved to regulate mitochondrial Mg via MRS2, regulate mitochondrial metabolism, induce macrophage M2 polarization, and inhibit M1 differentiation and osteoclast differentiation in vitro. Moreover, calvarial inflammatory osteolysis mouse model reveal that pBTO inhibit inflammatory bone resorption by modulating macrophage polarization and osteoclastogenesis via mitochondrial MRS2/Mg. These results indicates that pBTO may be a potential approach to treat inflammatory or infective osteolysis through "nanoelectric field - Mg transport - mitochondrial metabolism" signal axis in a convenient, wireless and non-invasive way.
炎症性骨吸收存在于常见的口腔颌面部疾病中。巨噬细胞在骨的炎症过程中起关键作用。研究表明，M1巨噬细胞会导致骨稳态和骨吸收紊乱，而M2巨噬细胞相关细胞因子会抑制破骨细胞生成。为抑制炎症性骨吸收，应找到一种促进M2极化、抑制M1极化和破骨细胞生成的方法。研究发现，巨噬细胞在M2分化过程中线粒体膜电位升高，而在M1分化和破骨细胞分化过程中降低。因此，我们推测利用电场调节巨噬细胞极化和破骨细胞分化或许是可行的。压电材料已被证明是一种能形成压电势的安全有效材料，但压电纳米材料和纳米电场在巨噬细胞M2分化和破骨细胞生成中的作用仍有待研究。因此，在本研究中，将极化压电纳米材料钛酸钡（pBTO）应用于巨噬细胞，以提供无线细胞内电场。结果证明，来自pBTO的无线细胞内电场可通过MRS2调节线粒体镁，调节线粒体代谢，诱导巨噬细胞M2极化，并在体外抑制M1分化和破骨细胞分化。此外，颅骨炎性骨溶解小鼠模型表明，pBTO通过线粒体MRS2/镁调节巨噬细胞极化和破骨细胞生成，从而抑制炎症性骨吸收。这些结果表明，pBTO可能是一种通过“纳米电场 - 镁转运 - 线粒体代谢”信号轴以方便、无线和非侵入性方式治疗炎性或感染性骨溶解的潜在方法。
