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

作　　者：Rui-Xue Jiang Nan Hu Yu-Wei Deng Long-Wei Hu Hao Gu Nan Luo Jin Wen Xin-Quan Jiang 

机构地区：[1]Department of Prosthodontics,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China [2]College of Stomatology,Shanghai Jiao Tong University,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai Key Laboratory of Stomatology,Shanghai Research Institute of Stomatology,Shanghai Engineering Research Center of Advanced Dental Technology and Materials,Shanghai 200125,China [3]Department of Endodontics,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Jiao Tong University,Shanghai 200011,China [4]Department of Oral and Maxillofacial-Head and Neck Oncology,Shanghai Ninth People’s Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200011,China [5]Department of Preventive Dentistry,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Jiao Tong University,Shanghai 200011,China

出　　处：《Zoological Research》2024年第2期367-380,共14页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China (81921002,81900970,82130027);Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZLCX20212400);Young Physician Innovation Team Project (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。

摘　　要：Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关 键 词：OSTEOPOROSIS SPERMINE RAC1 ZEBRAFISH MICE 

分 类 号：R580[医药卫生—内分泌] R-332[医药卫生—内科学]