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Ruixue Jiang, Nan Hu, Yuwei Deng, Longwei Hu, Hao Gu, Nan Luo, Jin Wen, Xinquan Jiang. Potential therapeutic role of spermine via Rac1 in osteoporosis: insights from zebrafish and mice. Zoological Research. doi: 10.24272/j.issn.2095-8137.2023.371
Citation: Ruixue Jiang, Nan Hu, Yuwei Deng, Longwei Hu, Hao Gu, Nan Luo, Jin Wen, Xinquan Jiang. Potential therapeutic role of spermine via Rac1 in osteoporosis: insights from zebrafish and mice. Zoological Research. doi: 10.24272/j.issn.2095-8137.2023.371

Potential therapeutic role of spermine via Rac1 in osteoporosis: insights from zebrafish and mice

doi: 10.24272/j.issn.2095-8137.2023.371
Funds:  This work was supported by the National Natural Science Foundation of China (No. 81921002, 81900970 and 82130027), the Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20212400), and the Young Physician Innovation Team Project (No. QC202003) of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Shanghai “Rising Stars of Medical Talent” Youth Development Program is also acknowledged.
  • Received Date: 2023-11-26
  • Accepted Date: 2024-01-12
  • Rev Recd Date: 2024-01-08
  • Published Online: 2024-01-16
  • Osteoporosis is a prevalent metabolic skeletal disease. While drug therapy is essential to prevent bone loss in osteoporosis patients, current treatments have limitations including side effects and high costs, necessitating the development of more efficient and safer targeted therapies. Utilizing a zebrafish larvae osteoporosis model, we explored the metabolite spermine’s influence on bone homeostasis. We found that spermine presented a dual action in osteoporotic zebrafish larvae: fostering bone formation and curtailing bone resorption. Moreover, spermine exhibited excellent biosafety while mitigating prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine also showcased protective attributes for the nervous systems of both zebrafish embryos and larvae. From the molecular level, we identified Rac1 as pivotal in mediating spermine’s anti-osteoporosis effects and P53 potentially worked downstream from Rac1. Furthermore, our experiments in mice models reinforced these findings, indicating that spermine not only ameliorates osteoporosis but also promotes bone formation and mineralization in healthy conditions, suggesting its strong potential as a bone-strengthening agent. This study underscores spermine’s beneficial role in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine emerge as promising candidates for new anti-osteoporosis drug development and as daily used bone-fortifying agents.
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