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通过模拟来研究微重力对hMSC向成骨细胞分化的影响,并利用相关信号通路的激活剂或抑制剂来调节这一分化过程.研究结果表明,在成骨细胞分化诱导条件下,微重力降低了hMSC向成骨细胞定向分化的能力,并且成骨细胞标记性基因的表达明显降低,Runt相关转录因子2(Runx2)的表达受到抑制.相反,过氧化物酶体增殖激活受体γ(PPARγ2)的表达则增加.同时,微重力也降低了ERK的磷酸化水平,而增加了p38MAPK的磷酸化水平.使用p38MAPK的抑制剂SB203580能够抑制p38MAPK的磷酸化,但不能降低PPARγ2的表达水平.骨形态发生蛋白(BMP)能增加Runx2的表达水平.成纤维细胞生长因子2(FGF2)增加了ERK的磷酸化水平,但也不能显著增加成骨细胞标记性基因的表达水平.采用BMP,FGF2和SB203580三种因子组合来调控微重力下的成骨细胞分化能力,结果表明三者的协同作用能显著逆转微重力对成骨细胞定向分化的生物学效应.研究结果还说明,模拟微重力应该是通过不同的细胞信号通路来抑制成骨细胞分化和提升脂肪细胞分化的.
The effects of microgravity on differentiation of hMSCs into osteoblasts were studied by means of simulation and the activation of agents or inhibitors of the relevant signaling pathways were used to regulate this differentiation process.The results showed that under the condition of osteoblast differentiation induction, The ability of hMSC to differentiate into osteoblasts was observed, and the expression of osteoblast marker gene was significantly decreased, and the expression of Runt-related transcription factor 2 (Runx2) was inhibited.On the contrary, peroxisome proliferator-activated receptor γ (PPARγ2 ), While microgravity reduced the phosphorylation of ERK and increased the phosphorylation of p38MAPK.Using p38MAPK inhibitor SB203580 can inhibit the phosphorylation of p38MAPK, but can not reduce the expression of PPARγ2. BMPs increased the expression of Runx2. FGF2 increased the phosphorylation level of ERK, but did not significantly increase the expression of osteoblast marker genes.Using BMP, FGF2 and SB203580 three kinds of factors to regulate the ability of osteoblast differentiation under microgravity, the results show that the synergy of the three can significantly reverse the impact of microgravity on osteoblast differentiation Biological effects.The results also show that simulated microgravity should be through different cell signaling pathways to inhibit osteoblast differentiation and enhance adipocyte differentiation.