Medial Osteochondral Defect Drives Matrix and Cell Pathology in Compartment-Matched Meniscus.

Abstract

Patients with cartilage defects often experience increased meniscal degeneration. It remains unclear whether meniscal damage occurs concurrently with cartilage injury or due to later joint pathology. Limited data exists on how isolated cartilage injuries affect meniscal structure and degeneration. In osteoarthritis models, alterations to the structure and composition of meniscal ECM components have been observed, including meniscus hypertrophy characterized by excessive glycosaminoglycan deposition and fibrochondrocyte rounding. Although proteoglycan deposition increases in early OA, the timing of GAG changes relative to collagen disruption remains unclear. This study examined the correlation between changes in local proteoglycan deposition, cell morphology, and the collagen network in the meniscus following cartilage damage using an in vivo rabbit model. A medial osteochondral defect was created on the femoral condyle of New Zealand white male rabbits, and menisci were harvested 12 weeks later. Our results indicate that a medial osteochondral defect drives pathology in the underlying meniscus, likely due to altered loading conditions. The medial menisci of defect joints exhibited increased proteoglycan deposition and hypertrophy, with increased cell roundness and area in regions of elevated GAGs. Local collagen architecture showed increased fiber diameter in the medial menisci of defect joints, which positively correlated with increased GAG coverage. Abnormal collagen structures were observed, including wider variations in fiber diameters and areas of small fibers with low second harmonic generation signals, indicating poorly organized collagen. A deeper understanding of GAG regulation and fibrochondrocyte pathology in injured meniscus tissue could aid in the development of therapeutics and inform disease progression.