Prostaglandin E2 receptor type 2-selective agonist prevents the degeneration of articular cartilage in rabbit knees with traumatic instability

The model of traumatic degeneration was established through transection of the anterior cruciate ligament and partial resection of the medial meniscus of the rabbits. Rabbits were divided into 5 groups; G-S (sham operation), G-C (no further treatment), G-0, G-80, and G-400 (single intra-articular administration of gelatin hydrogel containing 0, 80, and 400 μg of the specific EP2 agonist, ONO-8815Ly, respectively). Degeneration of the articular cartilage was evaluated at 2 or 12 weeks after the operation.ONO-8815Ly prevented cartilage degeneration at 2 weeks, which was associated with the inhibition of matrix metalloproteinase-13 (MMP-13) expression. The effect of ONO-8815Ly failed to last, and no effects were observed at 12 weeks after the operation.Stimulation of prostaglandin E2 (PGE2) via EP2 prevents degeneration of the articular cartilage during the early stages. With a system to deliver it long term, the EP2 agonist could be a new therapeutic tool for OA.Osteoarthritis (OA) is the single most common cause of disability in older adults [1]. It is a complex process involving a combination of cartilage degradation, repair, and inflammation. However, its pathogenesis is not yet fully understood [2]. Articular cartilage is composed of chondrocytes, and an extensive extracellular matrix (ECM). The major ECM components are type II collagen and aggrecan. In normal cartilage, catabolic and anabolic activities are in dynamic equilibrium. Chondrocytes can produce several catabolic cytokines such as IL-1 and TNF-α, which in turn induce the production of proteinases including matrix metalloproteinases (MMPs) and disintegrin-like and metalloproteinase with thrombospondin, that lead to the destruction of the matrix network [3,4]. Among the MMPs, MMP-13 (collagenase 3) plays a particularly important role in causing OA [5]. Indeed, transgenic mice carrying an inducible human MMP-13 gene develop pathological changes similar to those observed in human OA patients, when the trans