高脂饮食通过抑制Wnt/β-catenin信号介导对骨质疏松大鼠骨密度和骨修复的负面影响

Negative effects of high-fat diet on bone mineral density and bone repair in osteoporotic rats through suppression of Wnt/β-catenin signaling

目的评估高脂饮食(HFD)对骨质疏松大鼠骨密度(bone mineral density,BMD)及骨修复的影响并探讨可能的机制。方法将雌性SD大鼠随机分为三组:假手术卵巢切除组(Sham)、手术卵巢切除模型组(OVX)、手术卵巢切除模型+HFD(OVX+HFD);随后所有大鼠在双侧去卵巢手术或假手术后12周基础上制作双侧股骨干建立骨缺损模型,OVX+HFD组大鼠在股骨上接受HFD干预4周。随后使用影像学、血清学、骨生物力学以及基因水平检测来评估骨修复效果。结果与Sham组相比,OVX和OVX+HFD组的血清E2、ALP水平均显著降低(P<0.05),而TRAP水平均显著升高(P<0.05);OVX和OVX+HFD组之间有显著差异(P<0.05)。Micro-CT检测显示OVX+HFD组骨修复效果较OVX和Sham组明显降低;定量检测结果显示OVX+HFD组的BMD、Tb.N和Tb.Th显著小于OVX组(P<0.01),而Tb.Sp(P<0.05)在OVX+HFD组中明显大于在OVX组。生物力学显示HFD干预后明显降低了去卵巢大鼠骨缺损部位的机械强度,包括大鼠股骨的极限载荷、刚度、能量吸收和弹性模量(P均<0.05);基因检测表明与OVX组相比,OVX+HFD组Smad2、Smad3和GSK-3βmRNA表达显著增加(P<0.01),而Wnt1和β-cateninmRNA表达均显著降低(P<0.01)。结论HFD对骨质疏松状态下骨缺损愈合有负面影响,而这种影响可能是通过对Wnt/β-catenin信号传导抑制来实现的。

Objective To evaluate the effect of a high-fat diet(HFD)on bone mineral density and bone repair in osteoporotic rats and explore the possible mechanisms.Methods Female SD rats were randomly divided into three groups:sham surgical ovariectomy group(Sham),surgical ovariectomy model group(OVX),surgical ovariectomy model+HFD(OVX+HFD),all rats were subsequently ovarian removed on both sides Bilateral femoral shafts were created on the basis of 12 weeks after surgery or sham operation to establish a bone defect model.OVX+HFD rats received HFD intervention on the femur for 4 weeks.Imaging,serology,bone biomechanics,and genetic level testing were then used to evaluate the effect of bone repair.Results Compared with the Sham group,serum E2 and ALP levels in the OVX and OVX+HFD groups were significantly reduced(P<0.05),while TRAP levels were significantly increased(P<0.05);there was a significant difference between the OVX and OVX+HFD groups Difference(P<0.05).Micro-CT test showed that the effect of OVX+HFD bone repair was significantly lower than that of OVX and Sham groups;quantitative test result showed that BMD,Tb.N and Tb.Th is significantly smaller than the OVX group(P<0.01),while Tb.Sp(P<0.05)is significantly larger in the OVX+HFD group than in the OVX group.After the biomechanical HFD intervention,the mechanical strength of the bone defect site of ovariectomized rats was significantly reduced,including the ultimate load,stiffness,energy absorption and elastic modulus of the femur of the rat(all P<0.05);genetic testing showed that compared with the OVX group,The expressions of Smad2,Smad3 and GSK-3βmRNA in the OVX+HFD group were significantly increased(P<0.01),while Wnt1 andβ-catenin mRNA expression Significantly reduced(P<0.01).ConclusionHFD has a negative effect on the bone defect healing under osteoporosis,and this effect may be achieved by inhibiting Wnt/β-catenin signaling.