Articular chondrocytes from the knee and ankle have different sensitivities to shear strain

Abstract

Traumatic injury to synovial joints results in focal defects and proinflammatory changes in cartilage tissue, eventually leading to post-traumatic osteoarthritis (PTOA). Additionally, disparate incidence rates of PTOA occur between joints, particularly the knee and ankle. We hypothesize that differences in PTOA rates between knee and ankle cartilage are related to inherent differences in mechanical properties and chondrocyte sensitivity to mechanical loads. Our objective was to compare the effect of injury on the spatial patterns of cellular response between knee and ankle cartilage and relate these responses to changes in tissue mechanical properties. Cartilage explants of neonatal bovids from the talar dome of the ankle and femoral condyle of the knee were subjected to our ex vivo combined injury model which combines rapid impact injury and repetitive cartilage articulation. Explants were bisected and fluorescently stained to assess global and depth-dependent cell death, caspase activity, and mitochondrial depolarization. Explants were tested via confocal elastography to determine the local shear strain and shear modulus profile. Results showed that chondrocyte response differed between joints, with knee cartilage showing greater damage within the surface region. Additionally, ankle cartilage experienced a greater decrease in shear modulus post-injury compared to knee, causing depth-dependent shear strain to significantly increase (p < 0.0287). Furthermore, regression analyses relating cellular response to local shear strain revealed joint-specific differences in chondrocyte sensitivity, defined as the slope of cellular response versus shear strain, for cell death (knee: 873 vs ankle: 551), apoptosis (knee: 7779 vs ankle: 3577), and MT depolarization (knee: 848 vs ankle: 535).