Early Post‑Traumatic Osteoarthritis Features Greater Cartilage Extracellular Matrix Proteoglycan Loss Compared to the Pericellular Matrix

Proteoglycan loss in articular cartilage is a hallmark of post-traumatic osteoarthritis, and it can affect both chondrocyte biomechanics and tissue health. Previously, we found that 4 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 investigated whether this pattern is already present 2 weeks post-ACLT and whether changes in the PCM-to-ECM proteoglycan content ratio are associated with chondrocyte volumetric strain in superficial cartilage during tissue loading. Unilateral ACLT was performed in eight skeletally mature rabbits. Two weeks post-surgery, cartilage from load-bearing sites of the operated and contralateral knees was 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 via digital densitometry. Volumetric strain of superficial zone chondrocytes was also measured using two-photon confocal microscopy during compressive loading. In the superficial zone, the PCM-to-ECM proteoglycan content ratio was greater in the ACLT knees than in controls at the lateral tibial plateau (p = 0.043), but this was not clearly linked to changes in chondrocyte volumetric strain. 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 indicate preferential ECM proteoglycan loss relative to the PCM in early post-traumatic osteoarthritis, especially in the middle zone.