Cytokine Induced Metalloproteinase Expression and Activity Does Not Correlate with Focal Cartilage Pathology

Introduction. The carpal and metacarpophalangeal joints have a high incidence of disease in the equine athlete. Pathological change in the articular cartilage of these joints occurs in specific regions, particularly those areas exposed to high impact loading[1]. The ability of articular cartilage to resist compressive loading is largely due to the entrapment of high concentrations of aggrecan within the collagen fibrillar network. Depletion of aggrecan is one of the earliest events in cartilage degeneration in joint disease and has been associated with proteolysis within the interglobular domain of the molecule by both matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS-4 & 5)[Reviewed in 2]. Degradation of type II collagen, which occurs later in the disease process and may represent the point of irreversible cartilage damage, is due primarily to the action of collagenolytic MMPs[3]. The activity of aggrecanases and MMPs may be upregulated by inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) which are found in arthritic synovial fluids. It has been suggested that the difference in pathology between joint regions may be due to variability in the response of chondrocytes to these inflammatory cytokines[4]. To address this question, the expression and activity of the matrix degrading MMPs and aggrecanases was evaluated in cartilage derived from different weight bearing regions of normal equine joints in vitro models of early and late stage cartilage degradation associated with exposure interleukin-1 (IL-1), tumor necrosis factor (TNF), retinoic acid (RA), and IL-1 plus oncostatin M (OSM).