4.2 Article

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

Journal

JOURNAL OF BIOMATERIALS AND TISSUE ENGINEERING
Volume 12, Issue 12, Pages 2387-2394

Publisher

AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbt.2022.3211

Keywords

Cartilage Damage; Metformin; Bone Marrow Mesenchymal Stem Cells; Chondrocytes; Hypertrophy

Funding

  1. Natural Science Basic Research Program of Shaanxi Province [2021JQ-914, 2021JQ-916]
  2. Shaanxi Provincial People's Hospital Science and Technology Talent Support Program for Elite Talents [2021JY-38, 2021JY-50]

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This study aimed to investigate the effect of metformin on the differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs) into chondrocytes with a hypertrophic phenotype and the related mechanisms. The results showed that metformin inhibited the differentiation of BMSCs into chondrocytes with a hypertrophic phenotype and activated AMPK protein during this process.
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 metformin-containing 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.

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