The data presented in this study demonstrate that chondrocyte apoptosis is positively associated with degree of cartilage matrix damage and that the extent of apoptosis varies with cartilage zones and mechanical loading environment of the joint.

No abstract

SummaryOsteoarthritis (OA) is a chronic degenerative disease of diarthrodial joints most commonly affecting people over the age of forty. The causes of OA are still unknown and there is much debate in the literature as to the exact sequence of events that trigger the onset of the heterogeneous disease we recognise as OA.There is currently no consensus model for OA that naturally reflects human disease. Existing ex-vivo models do not incorporate the important inter-tissue communication between joint components required for disease progression and differences in size, anatomy, histology and biomechanics between different animal models makes translation to the human model very difficult. This narrative review highlights the advantages and disadvantages of the current models used to study OA. It discusses the challenges of producing a more reliable OA-model and proposes a direction for the development of a consensus model that reflects the natural environment of human OA.We suggest that a human osteochondral plug-based model may overcome many of the fundamental limitations associated with animal and in-vitro models based on isolated cells. Such a model will also provide a platform for the development and testing of targeted treatment and validation of novel OA markers directly on human tissues.

Objective. Chondrocyte apoptosis has been described in both human and experimentally induced osteoarthritis (OA), but its importance in the etiopathogenesis of OA is uncertain. The aims of this study were to determine the rate of chondrocyte apoptosis using different methods, and to investigate the relationship between this process and cartilage cellularity, expression of proapoptotic molecules, and expression of antiapoptotic molecules in articular cartilage obtained from patients with OA and from nonarthritic controls.Methods. We examined the extent of apoptosis in OA and nonarthritic control cartilage using expression of caspase-3, an enzyme that mediates the final stage of cell death by apoptosis, as well as the TUNEL method. We used immunohistochemistry to analyze the expression of a panel of proapoptotic and antiapoptotic molecules that regulate apoptosis in articular cartilage, in order to determine whether the rate of apoptosis is associated with the expression of these molecules.Results. The median (range) percentage of TUNEL-positive chondrocytes in knee OA cartilage (n ‫؍‬ 10 specimens), hip OA cartilage (n ‫؍‬ 9), and control cartilage (n ‫؍‬ 7) was 3.11 (1.67-3.67), 1.86 (1.22-2.89), and 0.39 (0.00-1.78), respectively. When all cartilage samples were pooled, apoptosis showed a strong inverse correlation with cellularity (r ‫؍‬ ؊0. Conclusion. The data suggest that apoptosis is increased, on average, 2-4-fold in OA cartilage. Considering that OA develops over many years, such an increase in the rate of apoptosis in the articular cartilage could play an important role in the disease process.