糖浓度及BMP4对小鼠诱导型多能干细胞成骨作用的研究

Effects of Glucose Level and BMP4 on Osteogenic Differentiation of Mouse Induced Pluripotent Stem Cells

诱导型多能干细胞(induced pluripotent stem cells,iPS cells)技术的建立为自体组织工程治疗带来了新的希望。鉴于糖尿病患者常伴有骨再生性障碍,该研究比较了不同葡萄糖浓度下小鼠iPS细胞的成骨能力,并探讨了骨形态蛋白4(bone morphogenetic protein 4,BMP4)在该过程中的作用。实验结果显示:成骨诱导21 d后,低糖组茜素红阳性细胞比例和成骨基因Runx2、Osteocalcin的表达水平显著高于高糖组和自发分化组(P<0.05);BMP4的添加提高了高糖组茜素红阳性细胞比例及Osteocalcin的表达水平(P<0.05),而对自发分化组细胞的成骨水平无影响。该结果表明:低葡萄糖含量对小鼠iPS细胞的骨向分化有促进作用,尽管BMP4可以提高高糖组小鼠iPS细胞的成骨能力,但仅在成骨分化条件下发挥作用。

Induced pluripotent stem （iPS） cell technology casts a light on autologous cell/tissue transplantation. Considering that diabetes is combined with delayed bone regeneration, so in this study, we investigated osteogenic capability of mouse iPS cells in the media with different glucose levels and evaluated effect of BMP4 （bone morphogenetic protein 4） on the osteogenic capability of mouse iPS cells. The results showed that, after 21 days of osteogenic induction, low-glucose-level group had a higher percentage of alizarin red S-positive cells and elevated mRNA levels of osteogenic genes, Runx2 and Osteocalcin, compared with those of the high-glucose-level group and spontaneous differentiation group （P〈0.05）; BMP4 treatment increased the percentage of alizarin red S-positive cells and expression level of Osteocalcin in high-glucose-level group （P〈0.05）, but had no effect in spontaneous differentiation group. The results indicated that low glucose level promoted osteogenetic differentiation of mouse iPS cells; Although BMP4 could enhance osteogenic ability in high-glucose-level group, it functioned specifically during osteogenesis.