A Study of the Effects of Metformin, a Biguanide Derivative, on Annulus Fibrosus and Nucleus Pulposus Cells

Özet

AIM: To investigate the effects of metformin, a drug used widely for the treatment of type 2 diabetes mellitus, on human primary cellcultures prepared from uninjured segment of disc material intervertebral disk tissues.MATERIAL and METHODS: Primary cell cultures were prepared using the tissues of six patients (three males and three females)who had undergone lumbar microdiscectomy and sequestrectomy. Untreated samples served as the control group, and metformintreated samples served as the experimental group. All the samples were evaluated using an inverted light microscope, acridineorange/propidium iodide staining (AO/PI), and a fluorescence microscope. The cytostatic and cytotoxic effects of metformin, whichwas administered to the samples using a commercial MTT assay kit, were also evaluated. The data obtained were statisticallyassessed, and the alpha significance value was accepted as less than 0.05. In addition, for the groups’ changes in the expressionsof chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1β (IL-1β) matrix metalloproteinase 7 (MMP-7),and matrix metalloproteinase 19 (MMP-19), genes related to the extracellular matrix synthesis and degradation were determinedusing gene-specific TaqMan Gene Expression Assays.RESULTS: The administration of the drug adversely affected nucleus pulposus (NP)/annulus fibrosus (AF) cells and extracellularmatrix–like structures. This was statistically significant (p<0.05).CONCLUSION: Clinicians should not disregard the adverse effects of metformin, which is used widely in clinical practice, on thecomponents of intervertebral disk tissues.