The Effect of Hyaluronic Acid on IL-1 beta-Induced Chondrocyte Apoptosis in a Rat Model of Osteoarthritis

The purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1 beta) and explore its mechanism. A rat in vitro model of osteoarthritis (OA) was established using 10 ng/mL IL-1 as a modulating and chondrocyte apoptosis inducing agent. Different doses of HA (10, 20, and 40 mu g/mL) were added I h prior to the addition of IL-1 beta to a monolayer culture of freshly isolated juvenile rat chondrocytes. The ratio of apoptotic cell death was evaluated by rhodamine- and propidum iodide double-labeling FACS analysis. The mitochondrial membrane potential of chodrocytes was evaluated by rhodamine-123 fluorescence. The mitochondrial function was evaluated through detecting the ATP production by a luciferase assay, The reverse transcription polymerase chain reaction (RT-PCR) was performed to measure mRNA expression levels of inducible oxide synthase (iNOS). HA could inhibit IL-1 beta-induced chondrocyte apoptosis in our cell culture model system. It was showed that addition of HA to the medium was able in a dose-dependent way to reduce the impairment of the mitochondrial membrane potential and to restore mitochondrial ATP production. This study shows that HA could suppress in a dose-dependent way chondrocyte apoptosis in our IL-1 beta-induced osteoarthritis model. The, suppression of inflammatory cytokine activity within the Joint might, be one important mechanism of the clinical action of intraarticular injection of HA in the treatment of OA. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:164:3-1648, 2008