mTOR signaling pathway-mediated autophagy involved in inhibition of osteoblast differentiation induced by cadmium in human bone marrow mesenchymal stem cells
10.3760/cma.j.cn112150-20210721-00697
- VernacularTitle:mTOR信号通路介导的自噬在镉抑制人骨髓间充质干细胞成骨分化中的作用
- Author:
Yangcong ZHANG
1
;
Qinzhi WEI
;
Youkun HU
;
Lu WU
;
Dongli LI
;
Zhaojie WANG
;
Qizhan LIU
;
Xingfen YANG
Author Information
1. 南方医科大学公共卫生学院 食物安全与健康研究中心，广州 510515
- Keywords:
Cadmium;
Autophagy;
Osteoblasts;
Human bone marrow mesenchymal stem cells
- From:
Chinese Journal of Preventive Medicine
2021;55(9):1123-1128
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of autophagy mediated by mTOR signaling pathway in the inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by cadmium.Methods:HBMSCs were divided into 0, 2.5 or 5.0 μmol/L groups according to the exposure dose of cadmium chloride (CdCl 2), and each group was treated for 1 day, 4 days and (or) 7 days. The ALP activity and mRNA and protein expression levels of osteogenesis markers (ALP, RUNX2 and OSTERIX), autophagy-related proteins (LC3 and Beclin-1) and mTOR signaling pathway related proteins (mTOR, p-mTOR and p-p70S6K) expression, alkaline phosphatase staining and alizarin red staining were detected. MHY 1485 was selected as the signaling pathway activator. The control group, CdCl 2 group (5.0 μmol/L), MHY 1485 group and CdCl 2+MHY 1485 combined treatment group were set. After 7 days of treatment, the expression levels of autophagy related proteins and mTOR signaling pathway related proteins of hBMSCs in each group were detected. Results:There was no significant difference in ALP activity between 0, 2.5 and 5.0 μmol/L groups on day 1 and 4 ( P>0.05); On day 7, compared with the 0 μmol/L group, the ALP activity, expression of osteogenic markers (ALP, RUNX2, OSTERIX) and mTOR signaling pathway related proteins (mTOR, p-mTOR, p-p70S6K) expression decreased in the 2.5 and 5.0 μmol/L group ( P<0.05). Compared with the 0 μmol/L group, the staining of the 2.5 and 5.0 μmol/L groups became lighter, and the formation of ALP and mineralized nodules was reduced. Compared with the CdCl 2 group, the autophagy related protein expression in the CdCl 2+MHY 1485 combined treatment group decreased, and the mTOR signaling pathway related protein expression increased. The difference was statistically significant ( P<0.05). Conclusion:The inhibition of osteogenic differentiation of hBMSCs by cadmium may be related to autophagy mediated by mTOR signaling pathway.
