Oral administration of a matrix metalloproteinase inhibitor, CGS 27023A, protects the cartilage proteoglycan matrix in a partial meniscectomy model of osteoarthritis in rabbits

Matrix metalloproteinases (MMP) are elevated in human osteoarthritic cartilage and in cartilage from rabbits with experimental osteoarthritis (OA) following partial meniscectomy. CGS 27023A is a MMP inhibitor that inhibits stromelysin, collagenase and gelatinase. CGS 27023A is an orally active inhibitor of stromelysin. CGS 27023A at 75 mu moles/kg p.o. inhibits release of proteoglycan into synovial fluid following intra-articular injection of stromelysin into rabbit knees. The purpose of these experiments was to determine whether CGS 27023A would inhibit cartilage proteoglycan loss in a partial meniscectomy model of osteoarthritis in rabbits. Doxycycline was used as a reference drug.