Expression profiling of metalloproteinases and inhibitors in cartilage

Objective  To profile the expression of all known members of the matrix metalloproteinase (MMP), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and tissue inhibitor of metalloproteinases (TIMPs) gene families in normal cartilage and that from patients with osteoarthritis (OA). Methods  Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR. Results  Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P < 0.001, MMP-13, MMP-28, ADAMTS-16; at P < 0.01, MMP-9, MMP-16, ADAMTS-2, ADAMTS-14 and at P < 0.05, MMP-2, TIMP-3, ADAMTS-12. Genes decreasing in expression in OA were: at P < 0.001, MMP-1, MMP-3, ADAMTS-1; at P < 0.01, MMP-10, TIMP-1, ADAMTS-9 and at P < 0.05, TIMP-4, ADAMTS-5, ADAMTS-15. Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage. Conclusion  This is the first comprehensive expression profile of all known MMP, ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies.