Chondrocyte death by apoptosis is associated with the initiation and severity of articular cartilage degradation

Abstract

To investigate the role of chondrocyte apoptosis in the initiation and severity of articular cartilage (AC) damage. Articular cartilage from equine metacarpophalangeal (MCP) (n = 13) and metatarsophalangeal (MTP) (n = 16) joints was used and each graded macroscopically for cartilage degradation (macroscopic osteoarthritis [OA] grade). Cartilage was sampled from six regions on the articular surface of both joint types and graded using a 'modified' Mankin scoring system. Apoptosis of chondrocytes in cartilage sections was assessed by expression of active caspase-3 using indirect immunohistochemistry. Apoptosis was found to increase significantly with macroscopic OA grade (P < 0.0001). There was a significant trend for increasing 'modified' Mankin score with increasing macroscopic OA grade (P < 0.0009). Apoptosis was significantly higher in the superficial zone than in the middle or deep zones (P < 0.01 and P < 0.001, respectively). The incidence of apoptosis correlated significantly with the early stages of microscopic cartilage damage ('modified' Mankin scores 0-3). Significant differences in overall apoptosis were noted when cartilage specimens with a 'modified' Mankin score of 3 were compared to grade 2 (P < 0.001), grade 1 (P < 0.001) and grade 0 (P < 0.05) specimens. However, no significant difference in overall apoptosis was noted between grade 3, 4 and 5 samples. The positive correlations of chondrocyte apoptosis with early stages of OA and severity of cartilage damage in the joints, suggest that this process is intrinsically linked to cartilage damage and may be associated with the initiation of cartilage degradation in OA.