mTORC1信号通路在张应力下对小鼠骨髓间充质细胞成骨分化的作用

The role of the mTORC1 signaling pathway during osteogenic differentiation of mouse bone marrow mesenchymal cells under tension stress

Objective To investigate the expression of the mTORC1 signaling pathway during the osteogenic differentiation of mouse bone marrow mesenchymal cells(BMMSCs) under cyclic uniaxial tension and explore its possible role.MethodsThe BMMSCs of mice were affected by uniaxial dynamic tensile force. Western blot was used to detect the expression changes of major molecules(mTOR, Raptor, S6 K) in the endogenous mTORC1 signaling pathway at 0, 1,2, 4, and 8 hours after stretching. Chemical colorimetry, ELISA and PCR were used to detect alkaline phosphatase(ALP), osteocalcin(OCN) and Runx2 mRNA, respectively. Then, inhibition, activation and control groups were established by administration of the drugs PP242, MHY1485 and PBS, respectively. Two hours after the stress, the expression of S6 K was detected by western blot, and the expression of the osteogenic signal was continuously detected by the above methods.Results Western blot analysis showed that the main molecules of the mTORC1 signaling pathwaywere all expressed within 8 hours after traction, and the highest expression was 2 hours after the stress. Compared withthose in the control group, the ALP activity and OCN expression decreased and the Runx2 m RNA levels increased afterthe m TORC1 signal pathway was inhibited(P < 0.001);ALP activity and OCN expression increased after the m TORC1 signal pathway was activated, while the Runx2 m RNA levels decreased(P < 0.001).ConclusionThe mTORC1 signal-ing pathway participates in the osteogenic differentiation of mouse BMMSCs under tension. The osteogenesis of BMMSCs under cyclic uniaxial tension would be enhanced if the mTORC1 signaling pathway was activated.