The Effect of Metformin on the Differentiation of Bone Marrow Mesenchymal Stem Cells into Chondrocytes with a Hypertrophic Phenotype

Abstract

Objective: To investigate the effect of metformin on the differentiation of Bone Marrow Mesenchymal Stem Cells into chondrocytes with a hypertrophic phenotype and related mechanisms. Methods: BMSCs were induced to differentiate into cartilage in vitro. The mRNA expression of chondrocyte markers and hypertrophic markers was analyzed. BMSCs were induced in vitro with metformincontaining and metformin-free chondrogenic medium, and Col2, SOX9, Runx2, and Col10 mRNA expression and AMPK protein expression in the metformin group and the control group were analyzed. Results: BMSCs were positive after induction into chondrocytes. The mRNA expression of Col2 and SOX9 was significantly increased on day 7. The mRNA expression of Runx2 and Col10 was significantly elevated at 14 days. Treatment with metformin at a concentration of 10 mM significantly reduced the cell viability of BMSCs. Significantly more Col2 and SOX9 mRNA expression was present in the experimental group than in the control group, whereas Runx2 and Col10 mRNA levels were significantly lower. In addition, AMPK protein expression significantly improved when compared to the control group. Conclusion: Metformin inhibits the differentiation of BMSCs into chondrocytes with a hypertrophic phenotype; metformin activates AMPK during inhibition of the differentiation of BMSCs into chondrocytes with a hypertrophic phenotype.