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

Abstract

Matrix metalloproteinases (MMP) are elevated in human osteoarthritic cartilage [1] and in cartilage from rabbits with experimental osteoarthritis (OA) following partial meniscectomy [2]. CGS 27023A is a M M P inhibitor that inhibits stromelysin, collagenase and gelatinase. CGS 27023A is an orally active inhibitor of stromelysin. CGS 27023A at 75 gmoles/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 [3]. Doxycycline was used as a reference drug [4].