Prolonged Excessive Weight Induces Spontaneous Meniscal Degeneration In Sows: A Preclinical Model For Obesity-Related Knee OA

Abstract

Abstract

Knee osteoarthritis (OA) and obesity are closely linked, with obesity being the primary risk factor for OA. This study used the medial meniscus of sows (250 kg, 4–6 years old) as a model for spontaneous OA, comparing them to lighter pigs (110 kg, 7–8 months old). The joints were collected according to the 3Rs principles (Replacement, Reduction and Refinement) and compared using macroscopic and microscopic analyses, as well as advanced imaging techniques. The results revealed more severe pathological changes in the sows. Micro-computed tomography analyses showed thickening of radial tie fibers in the sows, with volume fraction remaining similar between light pigs and sows. The highest percentage of tie fibers was found in the posterior horn. Magnetic resonance imaging did not detect any medial meniscal lesions. Histological analyses of the meniscal matrix confirmed disorganized collagen fibers and compromised matrix integrity. Additionally, Raman spectral analyses and immunofluorescence on the posterior horn, which is the most susceptible region for OA, revealed that light pigs exhibited a trend towards higher collagen crosslink ratios than sows, indicating differences in matrix maturity, particularly in the inner region. Finally, Substance P-positive nerve fibers grouped into corpuscles and concentrated in the outer third of the menisci in the sows, whereas in light pigs, only nerve fibers were observed. In conclusion, this study demonstrates that sows, develop spontaneous meniscal alterations and suggests that sows could be utilized as a sustainable animal model for studying OA providing insights into the relationship between obesity and joint health.