The purpose of this proposal is to study the synthesis of catabolic factors by articular cartilage in health and the disease state of osteoarthritis. The goal is to prove or disprove the hypothesis that osteoarthritis is initiated by enzymatic cartilage collagen degradation by increased collagenase activity. This postulate is that IL-1 stimulates collagenase activator protein (CAP), a latent metallo-protease of Mr 57,000 which, in turn, increases collagenase activity and joint destruction. Purified bovine collagenase has been demonstrated in the preliminary studies to have a near-absolute dependence upon CAP for activity. IL-1 was also found to markedly stimulate further CAP synthesis. Preliminary human studies demonstrated a 5 to 25-fold increase in CAP synthesis and collagenase activity by osteoarthritic as compared to normal cartilage. In this proposal, IL-1 and CAP synthesis by articular cartilage of normal and osteoarthritic human subjects will first be quantitated. Then active CAP synthesis, protein half-life and storage, and further stimulation of human articular cartilage of IL-1 and CAP will be quantitated in a large population of normal an osteoarthritic subjects by IL-1 LAF assay and a newly developed CAP RIA. A final study utilizing a well-defined rabbit model for osteoarthritis is designed to confirm the hypothesis by the quantitation of tissue, blood an synovial fluid IL-1 and CAP during and at the end-stage of osteoarthritis, which will be correlated with gross an histochemical tissue changes observed in the induced osteoarthritis.
| Awbrey, B J; Richlen, C A; Golpovar, M (1993) Human and bovine articular cartilage loading measured with a new resistive sensor: effects of protease degradation and osteoarthritis. Agents Actions Suppl 39:101-5 |
| Awbrey, B J; Kuong, S J; MacNeil, K L et al. (1993) The role of alpha-1-protease inhibitor (A1PI) in the inhibition of protease activity in human knee osteoarthritis. Agents Actions Suppl 39:167-71 |
