In vitro effects of oxytetracycline on matrix metalloproteinase-1 mRNA expression and on collagen gel contraction by cultured myofibroblasts obtained from the accessory ligament of foals.

The study explores how oxytetracycline, an antibiotic, impacts the matrix metalloproteinase-1 mRNA expression and contraction of collagen gel by myofibroblasts in foals. Findings suggest that oxytetracycline inhibits the structuring of collagen fibrils, possibly making developing ligaments and tendons more susceptible to stretching which could influence the treatment of flexural deformities in foals.

Study Overview

• The purpose of the research was to investigate the impact of oxytetracycline on matrix metalloproteinase-1 (MMP-1) mRNA expression and the contraction of collagen gel by myofibroblasts, which are cells involved in wound healing.
• This research was performed with a focus on potentially explaining the mechanism behind using oxytetracycline in the pharmacologic treatment of flexural deformities in foals (young horses).

Methodology

• The study used myofibroblasts from the accessory ligament of 6 foals, which were cultured in individual dishes with complete media (a kind of nutrient rich solution for the cells) and varying concentrations of oxytetracycline.
• The cells’ growth environment was a collagen gel scaffold, allowing for a three-dimensional cell culture model that mimics the in-vivo environment which cells naturally inhabit in the body. After 24 hours, the gels were released from the bottom of the plates to contract.
• An assessment of contraction was performed by taking photographs at multiple intervals after release. Additionally, further gels were harvested early for RNA isolation, to assess the impact on MMP-1 mRNA expression using reverse transcriptase-polymerase chain reaction, a method often used to detect specific RNA expression.

Results & Discussion

• Oxytetracycline was found to inhibit collagen gel contraction in a dose-dependent manner. It also resulted in a dose-dependent decrease in MMP-1 mRNA expression.
• This suggests that the compound restricts the structuring of collagen fibrils by equine myofibroblasts through an MMP-1 mediated mechanism.
• The impact on young foals could be critical as oxytetracycline administration might make their developing ligaments and tendons more vulnerable to elongation during normal weight-bearing and growth.
• Therefore, the inhibition of normal collagen organization could potentially provide the mechanistic explanation for the efficacy of oxytetracycline in the treatment of flexural deformities in foals.