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Self-powered intracellular nanogenerator attenuates inflammatory osteolysis through mitochondrial MRS2/Mg2+-mediated
Jiyuan Zuo1, Qining Guo1, Youzhun Fan2
1Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, China.
Abstract:
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 BaTiO3 (pBTO) is applied to macrophage cells to provide wireless intracellular electric field. Wireless intracellular electric field from pBTO is proved to regulate mitochondrial Mg2+ 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/Mg2+. These results indicates that pBTO may be a potential approach to treat inflammatory or infective osteolysis through "nanoelectric field - Mg2+ transport - mitochondrial metabolism" signal axis in a convenient, wireless and non-invasive way.
Insights
This study shows that piezoelectric nanomaterials can regulate macrophage polarization and inhibit bone resorption. This offers a potential non-invasive treatment for inflammatory bone loss by targeting mitochondrial pathways.
Area of Science:
- Biomaterials Science
- Immunology
- Cell Biology
Background:
- Macrophages are key players in inflammatory bone resorption, with M1 types promoting it and M2 types inhibiting it.
- Mitochondrial membrane potential changes during macrophage polarization and osteoclast differentiation, suggesting a potential regulatory target.
- Existing methods to control macrophage polarization and osteoclastogenesis are limited, necessitating novel approaches.
Purpose of the Study:
- To investigate the potential of piezoelectric nanomaterials to regulate macrophage polarization and osteoclast differentiation.
- To explore the role of nano-electric fields generated by polarized BaTiO3 (pBTO) in modulating macrophage behavior.
- To elucidate the underlying molecular mechanisms, specifically focusing on mitochondrial function and Mg2+ transport.
Main Methods:
- Application of polarized BaTiO3 (pBTO) nanomaterials to macrophage cells to induce wireless intracellular electric fields.
- In vitro assessment of macrophage polarization (M1 vs. M2) and osteoclast differentiation.
- In vivo studies using a calvarial inflammatory osteolysis mouse model.
- Analysis of mitochondrial Mg2+ regulation via MRS2 and its impact on mitochondrial metabolism.
Main Results:
- Wireless intracellular electric fields from pBTO successfully induced macrophage M2 polarization and inhibited M1 differentiation.
- pBTO treatment suppressed osteoclast differentiation and activity in vitro.
- In vivo experiments demonstrated that pBTO effectively inhibited inflammatory bone resorption in a mouse model.
- The mechanism involves the regulation of mitochondrial Mg2+ transport via MRS2, influencing mitochondrial metabolism.
Conclusions:
- Polarized BaTiO3 (pBTO) nanomaterials can modulate macrophage polarization and osteoclastogenesis through a nano-electric field mechanism.
- The pBTO-mediated effects are linked to the regulation of mitochondrial Mg2+/MRS2 signaling and metabolism.
- pBTO presents a promising, non-invasive therapeutic strategy for treating inflammatory and infectious osteolysis.
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