不同方式运动对生长期大鼠FGF、IGF信号及软骨内成骨的影响

Effects of different exercises on FGF,IGF signal and endochondral osteogenesis in growing rats

目的探索不同方式运动对生长期大鼠成纤维细胞生长因子(fibroblast growth factor,FGF)、胰岛素样生长因子(insulin-like growth factor,IGF)信号通路相关分子表达及软骨内成骨的影响。方法将生长期大鼠随机分为对照组、游泳组、跑台组和下跳组,进行6周的不同方式运动,利用软骨细胞原代分离、培养和染色技术,观察软骨细胞体外增殖,生长板切片染色,观察软骨细胞增殖肥大;利用RT-PCR、Western blot检测细胞因子mRNA和蛋白表达。结果(1)跑台运动和下跳运动有助于促进软骨细胞增殖和肥大,增加生长板肥大层的宽度,下跳运动更为明显;(2)FGF2 mRNA表达水平与对照组相比,游泳组差异无统计学意义(P>0.05),跑台组和下跳组显著降低(P<0.05);成纤维细胞生长因子受体1(fibroblast growth factor receptor,FGFR1)mRNA表达水平与对照组相比,跑台组和下跳组显著降低(P<0.01);成纤维细胞生长因子受体3(fibroblast growth factor receptor 3,FGFR3)mRNA表达水平与对照组相比,跑台组和下跳组显著降低(P<0.01);IGF-1 mRNA表达水平与对照组和游泳组相比,跑台组和下跳组均显著上调(P<0.05);IGF-1信号通过胰岛素样生长因子-1受体(Insulin like growth factor-1 receptor,IGF1R)mRNA表达水平与对照组相比,下跳组有统计学差异(P<0.05)。FGF2蛋白表达水平与对照组相比,游泳组无统计学差异(P>0.05),跑台组和下跳组都显著降低(P<0.01);IGF-1蛋白表达水平与对照组相比,游泳组无统计学差异(P>0.05),跑台组和下跳组显著增加(分别为P<0.05和<0.01),与游泳组相比,跑台组和下跳组均显著性增加(P<0.01)。结论下跳运动通过FGF、IGF信号通路,促进生长期大鼠生长板软骨细胞增殖与肥大,有利于软骨内成骨。

Objective To explore the effects of different forms of exercise on the expression of fibroblast growth factor(FGF),insulin-like growth factor(IGF)signal pathway related molecules and endochondral osteogenesis in growing rats.Methods Growing rats were randomly divided into control group,swimming group,treadmill group,and jumping group for 6 weeks.Chondrocyte proliferation in vitro,growth plate section staining and chondrocyte proliferation and hypertrophy were observed by primary isolation,culture and staining of chondrocytes.The expression of cytokine mRNA and protein was detected by RT-PCR and Western blot.Results(1)Treadmill exercise and jumping exercise were helpful to promote chondrocyte proliferation and hypertrophy,increase the width of hypertrophic layer of growth plate,and jumping exercise was more obvious.(2)Compared with the control group,the expression level of FGF2 mRNA in the swimming group had no significant difference(P>0.05),but decreased significantly in the treadmill running group and jumping group(P<0.05).Compared with the control group,the mRNA expression level of fibroblast growth factor receptor 1(FGFR1)in the treadmill running group and jumping down group decreased significantly(P<0.01);Compared with the control group,the mRNA expression level of fibroblast growth factor receptor 3(FGFR3)in treadmill running group and jumping group decreased significantly(P<0.01).Compared with the control group and swimming group,the expression level of IGF-1 mRNA in treadmill running group and jumping group was significantly up-regulated(P<0.05).The mRNA expression level of IGF-1 signal through insulin-like growth factor-1 receptor(IGF1R)in the jumping group was significantly higher than that in the control group(P<0.05).Compared with the control group,there was no significant difference in the expression level of FGF2 protein in the swimming group(P>0.05),but it was significantly lower in the treadmill running group and jumping group(P<0.01).Compared with the control group,there was no significant difference in the expression level of IGF-1 protein in the swimming group(P>0.05),but it was increased significantly in the treadmill group and the jumping group(P<0.05 and<0.01).Compared with the swimming group,the expression level of IGF-1 protein in the treadmill group and the jumping group increased significantly(P<0.01).Conclusion Jumping exercise promotes the proliferation and hypertrophy of growth plate chondrocytes in growing rats through FGF and IGF signal pathway,which is conducive to endochondral osteogenesis.