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 devel...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.展开更多
目的:考察RAC1基因多态性与Rac1-GTP蛋白表达水平的相关性。方法:选择182例健康汉族志愿者,经Taq Man-MGB探针等位基因分型技术测定RAC1基因中的4个标签单核苷酸多态性(tag single nucleotide polymorphism,tagSNPs)位点的基因型,采用...目的:考察RAC1基因多态性与Rac1-GTP蛋白表达水平的相关性。方法:选择182例健康汉族志愿者,经Taq Man-MGB探针等位基因分型技术测定RAC1基因中的4个标签单核苷酸多态性(tag single nucleotide polymorphism,tagSNPs)位点的基因型,采用酶联免疫吸附法测定其血浆中的Rac1-GTP蛋白表达水平。分析Rac1-GTP蛋白表达水平的分布特点;对RAC1基因4个tag-SNPs不同基因型间Rac1-GTP蛋白表达水平进行比较。结果:Rac1-GTP蛋白表达水平在健康汉族人群中呈现正偏态分布,女性中的表达水平高于男性(P<0.05);随着年龄的增加有降低的趋势,但差异无统计学意义(P>0.05)。Rac1-GTP蛋白表达水平在位点rs702482和rs10951982基因型间存在显著性差异(P<0.05),但在位点rs702483和rs6954996基因型间无统计学差异(P>0.05)。结论:在健康汉族人群中RAC1基因多态性存在影响Rac1-GTP蛋白表达水平的SNP位点。展开更多
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)+1 种基金Young Physician Innovation Team Project (QC202003)of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai“Rising Stars of Medical Talent”Youth Development Program is also acknowledged。
文摘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.
文摘目的:考察RAC1基因多态性与Rac1-GTP蛋白表达水平的相关性。方法:选择182例健康汉族志愿者,经Taq Man-MGB探针等位基因分型技术测定RAC1基因中的4个标签单核苷酸多态性(tag single nucleotide polymorphism,tagSNPs)位点的基因型,采用酶联免疫吸附法测定其血浆中的Rac1-GTP蛋白表达水平。分析Rac1-GTP蛋白表达水平的分布特点;对RAC1基因4个tag-SNPs不同基因型间Rac1-GTP蛋白表达水平进行比较。结果:Rac1-GTP蛋白表达水平在健康汉族人群中呈现正偏态分布,女性中的表达水平高于男性(P<0.05);随着年龄的增加有降低的趋势,但差异无统计学意义(P>0.05)。Rac1-GTP蛋白表达水平在位点rs702482和rs10951982基因型间存在显著性差异(P<0.05),但在位点rs702483和rs6954996基因型间无统计学差异(P>0.05)。结论:在健康汉族人群中RAC1基因多态性存在影响Rac1-GTP蛋白表达水平的SNP位点。
