Inhibition of interleukin-1-alpha-induced cartilage oligomeric matrix protein degradation in bovine articular cartilage by matrix metalloproteinase inhibitors - Potential role for matrix metalloproteinases in the generation of cartilage oligomeric matrix protein fragments in arthritic synovial fluid

Objective. To determine whether matrix metalloproteinases (MMPs) degrade ca rtilage oligomeric matrix protein (COMP) to produce fragments similar to th ose found in synovial fluid (SF) from patients with arthritis. Methods. COMP fragments were generated in vitro by treating (a) bovine arti cular cartilage with interleukin-1 alpha (IL-1 alpha), (b) purified bovine COMP with MMPs, and (c) articular cartilage with MMPs. The fragments genera ted in each case were analyzed by Western blot, using an antibody to the C- terminal heptadecapeptide of COMP, Results. IL-1 alpha stimulation of cartilage resulted in a fragmentation of COMP, which was inhibited by MMP inhibitors CGS 27023A and BB-94, Isolated , recombinant MMPs rapidly degraded purified COMP, as well as COMP residing in cartilage. Several COMP fragments produced in vitro had similar electro phoretic mobility to those in SF of patients with arthritis. Conclusion. MMPs may contribute to the COMP fragments found in vivo. Quanti tation of MMP-specific fragments may be useful in the evaluation of MMP inh ibitors in patients with arthritis.