Pericellular Matrix Proteoglycan Content is Less Affected in The Mid-Zone Cartilage in Early Post-Traumatic Osteoarthritis

Proteoglycan content changes in articular cartilage during post-traumatic osteoarthritis affect both chondrocyte biomechanics and tissue health. Previously, we found that four weeks after anterior cruciate ligament transection (ACLT) in rabbits, proteoglycan loss was less pronounced in the pericellular matrix (PCM) than in the extracellular matrix (ECM), resulting in a greater PCM-to-ECM proteoglycan content ratio compared to controls. Here, we investigate whether this pattern is already present two weeks post-ACLT and whether changes in the proteoglycan ratio relate to cell volumetric strain in the superficial zone during tissue loading. Unilateral ACLT was performed in eight skeletally mature rabbits. Two weeks post-surgery, cartilage from all load-bearing sites of the operated and contralateral knees were collected. Age-matched, non-operated knees from separate animals served as controls. Proteoglycan content in the chondrocyte microenvironment was analyzed in the superficial and middle zones of cartilage via digital densitometry. Volumetric strain of superficial zone cells was measured using two-photon confocal microscopy during indentation. In the superficial zone, the PCM-to-ECM proteoglycan content ratio was greater in the ACLT knees than in controls for the lateral tibial plateau (p = 0.043). However, this was not clearly linked to changes in cell volumetric strain. Interestingly, in the middle zone, the PCM-to-ECM proteoglycan content ratio was greater in the ACLT knees than in controls for the medial femoral condyle, femoral groove, and patella (p < 0.05). These results suggest that, in early post-traumatic osteoarthritis, proteoglycan loss is less severe in the PCM than in the ECM, especially in the middle cartilage zone.