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The Study Of Icariin In Regulating The Osteogenesis And Adipogenesis Of BMSCs For The Treatment Of Steroid-induced Osteonecrosis Of The Femoral Head

Posted on:2018-02-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z F HuangFull Text:PDF
GTID:1314330515983359Subject:Surgery
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Objective:We aim to explore the ability of proliferation,osteogenic differentiation and adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in SD rats exposed to MPS.This study is to investigate the signal pathway expression level of key factors of osteogenic differentiation and adipogenic differentiation on MPS.Methods:The original BMSCs were isolated and extracted based on the classical method.BMSCs were identified by flow cytometry.The proliferation ability of BMSCs was measured under different concentrations of MPS.The effects of different concentrations of MPS on osteogenic differentiation and adipogenic differentiation of BMSCs were further analyzed.Results:The growth of BMSCs was inhibited obviously,the mRNA expression of Caspase-3 was increased and the Bcl-2 expression was decreased with the increase of MPS concentration.On the one hand,ALP activity and mineralized nodule formation and osteogenic differentiation related factor Runx2,OC,ALP,BMP2 expression level of BMSCs were inhibited by MPS;on the other hand,TG content,lipid droplet formation and the expression level of adipogenic differentiation related factor PPARy were increased by MPS.Conclusions:MPS weekened the number and function of BMSCs which leading to abnormal differentiation between osteoblasts and adipocytes and balance disorder.This is a key point in the pathogenesis of glucocorticoid induced osteonecrosis of the femoral head.Objective:We aim to investigate whether the ability of proliferation,osteogenic differentiation and adipogenic differentiation of BMSCs could be recovery and restore the dynamic balance between osteogenesis and adipogenesis.Methods:We first determined the effects of different concentrations of Icariin on the proliferation of BMSCs.Then,we tested the effects of Icariin on the osteogenic differentiation and adipogenic differentiation of BMSCs exposed to MPS.Lastly,The expression of the related pathway products of osteogenic differentiation and adipogenic differentiation was determined by molecular mechanism.Results:Compared with the control group,Icariin increased the proliferation activity of BMSCs.Icariin could partly antagonize the inhibitory effect of MPS on the proliferation of BMSCs and decreased the mRNA level of caspase-3 of BMSCs treated with MPS.Compared with the MPS group,Icariin not only partly antagonized inhibitory effect of MPS on osteogenic differentiation of BMSCs that increasing the ALP activity,mineralized nodules formation and expression level of osteogenic differentiation related factors Runx2,OC,ALP,BMP2,but also inhibited enhancing effect of MPS on adipogenic differentiation of BMSCs that decreasing the contect of TG,lipid droplets formation and expression level of adipogenic differentiation related factor PPAR?.Conclusions:Icariin can increase the proliferative activity of BMSCs,partially restore the function of BMSCs and the balance of osteogenic and adipogenic differentiation.Objective:We aim to further evaluate Icariin on prevention and treatment effect of glucocorticoid induced osteonecrosis of the femoral head in vivo.The purpose of this study was find new prevention and treatment measures for early stage of glucocorticoid induced osteonecrosis of femoral head.Methods:Thirty SD female rats were randomly divided into three groups:blank group(Control Group),model group(MPS)and treatment group(ICA+MPS Group),ten rats in each group.After 12 weeks of modeling,serum biochemistry,histopathology and MicroCT imaging were performed.Results:At 12 weeks,the incidence of osteonecrosis of the femoral head in the blank group,the model group and the treatment group was 0(0/10),80%(8/10),30%(3/10),(3/10),respectively.Results of histology showed that bone lacuna,bone trabecula and bone marrow necrosis were improved,the number of lipid droplets decreased when compared with the model group.The serum ALP level increased and TG content decreased in the treatment group(P<0.05).Results of microCT showed that BMD,bone volume/total volume(BV/TV),bone volume/total volume(BS/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular spacing(Tb.Sp)in blank group were significantly higher than the model group or the treatment group,the above index in treatment group showed higher than the model group.Conclusions:Icariin can effectively prevent and treat early stage of glucocorticoid induced osteonecrosis of the femoral head,remodel bone tissue and delay disease progression.
Keywords/Search Tags:Glucocorticoid induced osteonecrosis of the femoral head, Bone marrow mesenchymal stem cells, Osteogenic differentiation, Adipogenic differentiation, Icariin, Animal models, Treatment
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