Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in...Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.展开更多
目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性...目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。展开更多
基金Beijing Natural Science Foundation,Grant/Award Number:L222145CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2019-I2M-5-038+2 种基金Clinical Medicine Plus X-Young Scholars Project,Peking Universitythe Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2023LCXQ017National Natural Science Foundation of China,Grant/Award Number:81700935。
文摘Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.
文摘目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。
