IGF-1 c.258同义突变对破骨细胞增殖分化及相关通路的影响

Effects of IGF-1 c.258 synonymous mutations on osteoclast proliferation,differentiation and related pathways

研究发现IGF-1同义突变影响骨形成及骨吸收,破骨细胞是介导骨吸收的关键细胞。为分析同义突变对破骨细胞增殖分化及相关通路的影响,本研究以IGF-1 c.258A>G小鼠为实验对象,分离培养破骨前体细胞并诱导分化,以检测不同基因型破骨细胞增殖和骨吸收功能,通过qRT-PCR检测相关基因及相关通路基因表达量。结果显示,OCL-G的IGF-1表达量显著高于OCL-A(P<0.01);NFATc1与LPAR基因表达量无显著性差异(P>0.05);而ephrinB2基因表达量OCL-G较高(P<0.01);Sema4D基因表达量同样OCL-G较高(P<0.001);At6v0d2则与之相反(P<0.001)。破骨细胞增殖与骨吸收功能变化不显著。结果表明,本试验证实了IGF-1同义突变影响了IGF-1基因与相关通路基因的表达,并解释了破骨细胞增殖与骨吸收没有显著变化的原因,为进一步研究IGF-1同义突变对破骨细胞的影响奠定了基础。

Studies have found that the synonymous mutation of IGF-1 affects bone formation and resorption,and osteoclasts are the key to mediate bone resorption.In order to analyze the effect of synonymous mutation on osteoclast proliferation,differentiation and related pathways,the mice with synonymous mutation of IGF-1 were used as the experimental subjects.Osteoclast precursor cells were isolated and cultured,and osteoclast differentiation was induced to detect the proliferation and bone resorption function of different genotypes of osteoclasts.The results showed that the expression of IGF-1 in OCL-G was significantly higher than that in OCL-A(P<0.01).There was no significant difference in gene expression between NFATc1 and LPAR(P>0.05).However,the ephrinB2 gene expression was higher in OCL-G(P<0.01).The expression of Sema4D gene was also higher in OCL-G(P<0.001).At6v0d2 showed the opposite pattern(P<0.001).There was no significant change in the proliferation of osteoclasts and bone resorption function.In summary,IGF-1 synonymous mutation affects the expression of IGF gene and related pathway genes.It also explains the reason why there is no significant change in osteoclast proliferation and bone resorption,which lay a foundation for further study on the effect of IGF-1 synonymous mutation on osteoclasts.