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-  2018 

Sonic Hedgehog串话人胰岛素样生长因子-1介导的信号通路促进髁突肥大软骨过生长的机制 Mechanism of Cooperation Between Sonic Hedgehog and Insulin-Like Growth Factor-1 in Promoting Condylar Hyperplasia Cartilage Overgrowth

Keywords: 髁突肥大,软骨细胞,Sonic Hedgehog,胰岛素样生长因子-1

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Abstract:

目的:探讨Sonic hedgehog(Shh)与人胰岛素样生长因子-1(IGF-1)介导的信号通路在促进髁突肥大病理进程中的作用及串话机制。方法:选取正常髁突及髁突肥大软骨标本,以及骨髓间充质细胞(BMSC),体外分离进行平板及三维培养,按不同的实验目的划分为不同的比较组,每个比较组按不同的实验目的各含不同的刺激组,分别添加IGF-1,NVP-AEW541,Cyclpamine,U0126/LY294002因子等单独或联合刺激,孵育后收获细胞进行计数或进行real-time PCR或Western Blot实验。结果:髁突肥大软骨细胞中加入Cyclopamine,COLX、PCNA、MMP-13基因和蛋白表达量明显降低,而cleaved-caspase-3明显升高(P<0.05),细胞数目明显降低(P<0.05)。添加Cyclopamine刺激的髁突肥大软骨细胞,磷酸化状态P-AKT和P-ERK均显著降低(P<0.05),Cleavedcaspase-3蛋白表达水平显著升高(P<0.05)。在BMSC加强IGF-1及Shh的刺激后COLX、COL2、PCNA、MMP-13、BCL2基因的表达量均明显升高(P<0.05)。单独加强IGF-1或Shh刺激,均可引起另一信号通路的加强(P<0.05)。结论:Shh与IGF-1介导的信号通路存在串话机制促进肥大髁突软骨细胞及间充质细胞增殖、分化及凋亡的作用,并通过PI3-K AKT和MAPK-ERK通路发挥作用

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