Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification
Simulated microgravity (SMG) poses substantial challenges to astronaut health, particularly impacting osteoblast function and leading to disuse osteoporosis. This study investigates the adverse effects of SMG on osteoblasts, focusing on changes in mitochondrial dynamics and their consequent effects...
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| Language: | English |
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0602 |
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| author | Qiusheng Shi Yaxin Song Jingqi Cao Jing Na Zhijie Yang Xinyuan Chen Ziyi Wang Yubo Fan Lisha Zheng |
| author_facet | Qiusheng Shi Yaxin Song Jingqi Cao Jing Na Zhijie Yang Xinyuan Chen Ziyi Wang Yubo Fan Lisha Zheng |
| author_sort | Qiusheng Shi |
| collection | DOAJ |
| description | Simulated microgravity (SMG) poses substantial challenges to astronaut health, particularly impacting osteoblast function and leading to disuse osteoporosis. This study investigates the adverse effects of SMG on osteoblasts, focusing on changes in mitochondrial dynamics and their consequent effects on cellular energy metabolism and mechanotransduction pathways. We discovered that SMG markedly reduced the expression of osteoblast differentiation markers and promoted mitochondrial fission, as indicated by an increase in punctate mitochondria, a decrease in mitochondrial length, and a reduction in cristae density. These mitochondrial alterations are linked to elevated reactive oxygen species levels, a decrease in ΔΨm, and a metabolic shift from oxidative phosphorylation to glycolysis, resulting in decreased adenosine triphosphate production, which are all indicative of mitochondrial dysfunction. Our results showed that treatment with mitochondrial division inhibitor-1 (mdivi-1), a mitochondrial fission inhibitor, effectively inhibited these SMG-induced effects, thereby maintaining mitochondrial structure and function and promoting osteoblast differentiation. Furthermore, SMG disrupted critical mechanotransduction processes, by affecting paxillin expression, the RhoA–ROCK–Myosin II pathway, and actin dynamics, which subsequently altered nuclear morphology and disrupted Yes-associated protein signaling. Notably, treatment with mdivi-1 prevented these disruptions in mechanotransduction pathways. Moreover, our study showed that SMG-induced chromatin remodeling and histone methylation, which are epigenetic barriers to osteogenic differentiation, can be reversed by targeting mitochondrial fission, further highlighting the significance of mitochondrial dynamics in osteoblast function in an SMG environment. Therefore, targeting mitochondrial fission emerges as a promising therapeutic strategy to alleviate osteoblast dysfunction under SMG conditions, providing novel approaches to maintain bone health during prolonged space missions and safeguard the astronaut well-being. |
| format | Article |
| id | doaj-art-876dabbcb34148ccb1761ca0f12a3f48 |
| institution | Kabale University |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-876dabbcb34148ccb1761ca0f12a3f482025-02-04T08:00:29ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0602Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic ModificationQiusheng Shi0Yaxin Song1Jingqi Cao2Jing Na3Zhijie Yang4Xinyuan Chen5Ziyi Wang6Yubo Fan7Lisha Zheng8Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.Simulated microgravity (SMG) poses substantial challenges to astronaut health, particularly impacting osteoblast function and leading to disuse osteoporosis. This study investigates the adverse effects of SMG on osteoblasts, focusing on changes in mitochondrial dynamics and their consequent effects on cellular energy metabolism and mechanotransduction pathways. We discovered that SMG markedly reduced the expression of osteoblast differentiation markers and promoted mitochondrial fission, as indicated by an increase in punctate mitochondria, a decrease in mitochondrial length, and a reduction in cristae density. These mitochondrial alterations are linked to elevated reactive oxygen species levels, a decrease in ΔΨm, and a metabolic shift from oxidative phosphorylation to glycolysis, resulting in decreased adenosine triphosphate production, which are all indicative of mitochondrial dysfunction. Our results showed that treatment with mitochondrial division inhibitor-1 (mdivi-1), a mitochondrial fission inhibitor, effectively inhibited these SMG-induced effects, thereby maintaining mitochondrial structure and function and promoting osteoblast differentiation. Furthermore, SMG disrupted critical mechanotransduction processes, by affecting paxillin expression, the RhoA–ROCK–Myosin II pathway, and actin dynamics, which subsequently altered nuclear morphology and disrupted Yes-associated protein signaling. Notably, treatment with mdivi-1 prevented these disruptions in mechanotransduction pathways. Moreover, our study showed that SMG-induced chromatin remodeling and histone methylation, which are epigenetic barriers to osteogenic differentiation, can be reversed by targeting mitochondrial fission, further highlighting the significance of mitochondrial dynamics in osteoblast function in an SMG environment. Therefore, targeting mitochondrial fission emerges as a promising therapeutic strategy to alleviate osteoblast dysfunction under SMG conditions, providing novel approaches to maintain bone health during prolonged space missions and safeguard the astronaut well-being.https://spj.science.org/doi/10.34133/research.0602 |
| spellingShingle | Qiusheng Shi Yaxin Song Jingqi Cao Jing Na Zhijie Yang Xinyuan Chen Ziyi Wang Yubo Fan Lisha Zheng Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification Research |
| title | Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification |
| title_full | Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification |
| title_fullStr | Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification |
| title_full_unstemmed | Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification |
| title_short | Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification |
| title_sort | inhibition of mitochondrial fission reverses simulated microgravity induced osteoblast dysfunction by enhancing mechanotransduction and epigenetic modification |
| url | https://spj.science.org/doi/10.34133/research.0602 |
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