调控miR-152对骨质疏松大鼠模型骨生物力学、骨重建平衡及骨组织Hedgehog信号通路的影响

Effect of regulating miR-152 on bone biomechanics,bone remodeling balance and Hedgehog signal pathway in osteoporosis rat model

目的:探讨调控微小RNA-152(miR-152)对骨质疏松大鼠模型骨生物力学、骨重建平衡及骨组织Hedgehog信号通路的影响。方法:将32只SD大鼠分为四组,对照组8只(正常大鼠),其他大鼠建立骨质疏松模型,按miR-152表达,分为模型组(8只)、过表达组(8只)及沉默组(8只),比较四组大鼠骨生物力学、骨重建平衡及骨组织Hedgehog信号通路改变情况。结果:与对照组相比,建立骨质疏松模型后大鼠血钙、碱性磷酸酶(ALP)表达明显下降,血磷明显升高,股骨密度值、骨矿物质含量均明显降低(均P<0.05),其中沉默组股骨密度值、骨矿物质含量、ALP表达高于模型组、过表达组,血钙、血磷低于模型组、过表达组(均P<0.05)。建立骨质疏松模型后大鼠成骨特异性转录因子(CBF-α_(1))、Ⅰ型前胶原氨基酸前肽(PINP)、骨吸收标记物(CTX-Ⅰ)、蛋白音猬因子(SHH)、胶质瘤相关癌基因1蛋白(GLI-1)表达以及最大荷载、刚度、骨保护蛋白(OPG)、骨形态发生蛋白2(BPM-2)表达均明显下降,其中沉默组高于模型组、过表达组(均P<0.05)。结论:miR-152通过调控骨组织Hedgehog信号通路,起到增加骨生物力学,促使骨重建平衡的作用。

Objective:To analyze the effects of regulating microRNA-152(miR-152)on bone biomechanics,bone remodeling balance and bone Hedgehog signal pathway in osteoporosis rat model.Methods:Thirty-two SD rats were divided into 4 groups.Eight rats was in the control group(normal rats).Other rats were used to establish osteoporosis models,and they were divided into model group(8 rats),overexpression group(8 rats)and silencing group(8 rats)according to the expression of miR-152.The changes of bone biomechanics,bone remodeling balance and Hedgehog signal pathway in bone tissue of the four groups were compared.Results:Compared with the control group,after establishing the osteoporosis model,the expression of blood calcium and ALP decreased significantly,blood phosphorus increased significantly,and the femoral density and bone mineral content decreased significantly(all P<0.05).The femoral density,bone mineral content and ALP expression in the silencing group were higher than those in the model group and overexpression group,while the blood calcium and phosphorus were lower than those in the model group and overexpression group(all P<0.05).The expression of CBF-α_(1),PINP,CTX-Ⅰ,SHH,GLI-1,OPG and BPM-2 were significantly decreased after the osteoporosis model was established,and those of the silencing group were higher than those of the model group and the overexpression group(all P<0.05).Conclusion:MiR-152 can increase bone biomechanics and promote bone reconstruction and balance by regulating Hedgehog signal pathway in bone tissue.