中华骨质疏松和骨矿盐疾病杂志2023，Vol.16Issue(5)：468-475,8.DOI:10.3969/j.issn.1674-2591.2023.05.007
雷帕霉素对铁蓄积高转换骨质疏松小鼠骨生成的影响
Effect of rapamycin on osteogenesis in high-turnover osteoporosis mice with iron accumulation
摘要
Abstract
Objective To study the osteogenic effect of rapamycin,an inhibitor of mTOR,on high-turnover oste-oporosis with iron accumulation.Methods Sixteen 8-week-old wild(Wt)female mice and forty-eight 8-week-old(△Hep)transgenic female mice were ovariectomized(OVX).They were divided into four groups(Wt+OVX group,△Hep+OVX group,△Hep+OVX+Carboxymethylcellulose(CMC)group,and △Hep+OVX+Rapa group).Rapa with a dose of 3 mg/(kg·d)was injected intraperitoneally for 2 months.CMC was the solvent of Rapa,and the dose and duration of in-jection were the same as△Hep+OVX+Rapa group.After the last injection,four groups of mice were executed to collect ser-um and bone tissue samples.Bone mass,bone mineral density(BMD)and other indexes of femur were measured by micro-CT.Bone mass and trabecular structure were measured by scanning electron microscopy(SEM)and HE staining.The femo-ral bending modulus of elasticity,bending energy,maximum bending stress,and bending rigidity coefficient were measured by biomechanical experiments.The expression of serum osteogenic-indexes[alkaline phosphatase(ALP),procollagenⅠN-terminal propeptide(P1NP),osteocalcin(OCN)]were detected by ELISA,and the expression of osteogenic genes[runt-related transcription factor 2(Runx2),transcription factor SP7(SP7),ALP]in bone were detected by RT-PCR.Results Micro-CT of femer showed that the BMD,bone volume to total volume(BV/TV),trabecular number(TB.N),trabecular thickness(TB.Th)and connection density(ConnD)significantly decreased but trabecular sepa-ration(TB.Sp),structure model index(SMI)significantly increased in △Hep+OVX group and △Hep+OVX+CMC group by comparing with Wt+OVX group.The BMD,BV/TV,TB.N,TB.Th,and ConnD significantly increased but TB.Sp,SMI significantly decreased in △Hep+OVX+Rapa group by comparing with △Hep+OVX group and △Hep+OVX+CMC group(P＜0.05).Compared with Wt+OVX group,femoral scanning electron microscopy and tibial HE staining showed that the bone mass and trabecular bone in△Hep+OVX group and△Hep+OVX+CMC group decreased significantly,but they were improved significantly after rapamycin treatment(P＜0.05).Compared with Wt+OVX group,the femoral bending modulus of elasticity,bending energy,maximum bending stress,and bending rigidity coef-ficient in △Hep+OVX group and△Hep+OVX+CMC group decreased significantly,and recovered significantly after ra-pamycin injection(P＜0.05).Compared with △Wt+OVX group,the expression of serum osteogenic-indexes(ALP,P1NP,OCN)and bony osteogenic-genes(Runx2,SP7,ALP)in △Hep+OVX group and △Hep+OVX+CMC group decreased significantly,but increased significantly after rapamycin intervention(P＜0.05).Conclusion Rapamycin,which has positive effect on osteogenesis,can improve bone mass and osteoblastic activity in high-turnover osteoporosis with iron accumulation.关键词
铁蓄积/雷帕霉素靶蛋白/雷帕霉素/成骨细胞/骨生成Key words
iron accumulation/mammalian target of rapamycin/rapamycin/osteoblasts/osteogenesis分类
医药卫生引用本文复制引用
吴加东,徐又佳,季宏建,孙焕建..雷帕霉素对铁蓄积高转换骨质疏松小鼠骨生成的影响[J].中华骨质疏松和骨矿盐疾病杂志,2023,16(5):468-475,8.基金项目
江苏医药职业学院临床学院(盐城市第三人民医院)专项科研发展基金(20219125) （盐城市第三人民医院）
