Researcher(s)
- Rachel Perry, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Xin Lucas Lu, Mechanical Engineering, University of Delaware
Abstract
Metformin’s Effect on Bovine Articular Cartilage Chondrocyte Metabolic Activity
Introduction: Metformin, an anti-inflammatory drug commonly used to treat type two diabetes, is believed to have promising effects on articular cartilage, specifically ones damaged by osteoarthritis. Osteoarthritis is a degenerative disease that destroys the integrity of chondrocyte extracellular matrix (ECM) by decreasing levels of vital cartilage functions, such as glycosaminoglycan (GAG) content, collagen synthesis, and mitochondrial activity. Despite the current literature investigating metformin on chondrocytes, there is an apparent lack of in vitro modeling and dosage studies of metformin on metabolic activity. Hence, the aim of this study was to evaluate the effect of different concentrations of metformin on young and healthy or damaged chondrocytes.
Methods: Top zone articular cartilage explants were harvested from bovine knee joints (1-2 months old, mixed side and gender), and were cultured in Chondrogenic Medium for 2 days before experiments. Inflammatory (interleukin‐1β) challenged cartilage samples were treated with metformin, doses ranging from 10uM to 10mM. To quantify the amount of GAG synthesis, GAG loss, and collagen synthesis, click-chemistry-based protocols were performed.
Results: All concentrations of metformin were not significantly different from the IL1β group. For the 1mM and 10mM concentrations, metformin increased GAG loss when combined with IL1β. Collagen synthesis decreased with the addition of metformin whereas GAG synthesis increased; however, this difference was not significant.
Conclusions: Metformin, despite its promising applications on articular cartilage, failed to significantly increase GAG and collagen synthesis and failed to reduce GAG loss for all doses. More GAG loss was observed in higher doses of 1mM or 10mM compared to the IL1β group.
Significance: These findings suggest that metformin doses of 10uM to 10mM are not the most efficacious options for reducing GAG loss and increasing collagen and GAG synthesis.