Novel selective MMP-13 inhibitors are associated with reduced joint damage and increased cartilage regeneration during osteoarthritis progression

Abstract

Osteoarthritis (OA) is a common degenerative disease characterized by the destruction of articular cartilage and chronic inflammation of surrounding tissues. Matrix metalloprotein- ase-13 (MMP-13) plays a pivotal role in cartilage degradation through its ability to cleave type II collagen comprising an attractive target during OA progression. New classed of very potent and highly selective MMP-13 inhibitors showed increased capacities in the block- age of IL-1/OSM induced type II collagen degradation in bovine explants and human OA cartilage samples indicating potential chondroprotective and regenerative efficacy. The elu- cidation of the pathophysiological processes and the understanding of the mechanisms of MMP-13 regulation in OA and the development of MMP-13 selective inhibitors may provide a potential target therapeutic option for OA cartilage prevention and regeneration.