Characterization of OA development between sexes in the rat medial meniscal transection model

Abstract

Objective: Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While clear sex differences exist in human OA development, most pre-clinical research has been conducted solely in male animals, limiting generalizability of findings to both sexes. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery. Design: An MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure. Results: Analysis of medial 1/3 articular cartilage, showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Both male and female MMT groups also saw increased subchondral bone mineral density and larger osteophyte volumes. Significant interactions between sex and OA development were seen in normalized cartilage volume (larger in females), and normalized total osteophyte volumes (larger in males). Conclusion: This study demonstrates the viability of both sexes in the rat MMT preclinical OA model. Though clear differences exist, this model can be used to model OA development and evaluate sex as a factor in the efficacy of OA therapeutics.