Effects of Hyaluronic Acid and Statins against LPS-induced Inflammation and Apoptosis in Porcine Articular Chondrocytes

Intra-articular therapy with hyaluronic acid (HA) is commonly used in osteoarthritis treatment. Lipid-lowering drug statins have been shown to have pleiotropic effects such as anti-inflammatory and reduces matrix-degrading enzymes expression. The objective of this study is to examine the therapeutic effects of statin and hyaluronic acid within an in vitro osteoarthritis model. 0.1mg/ml of HA (ARTZ Dispo®) in combination with different doses (5μM, 10μM, and 50μM) of simvastatin (lipophilic) or pravastatinhydrophilic) were treated to LPS-induced inflammation and apoptosis in porcine articular chondrocyes. We evaluated cytotoxicity, cell proliferation, NF-κB activity, NOroduction, DNA fragmentation, and gene expression of IL-1β, TNF-α, IL-6, iNOS, caspase 3, MMP-1, MMP-13, and COL2A1. Although results showed that the expressionf IL-1β, IL-6, iNOS, caspase 3, MMP-1, and MMP-13 were found significantly decreased when treated with HA in combination with 50μM simvastatin (H50S). However, simvastatin shown to have cytotoxicity effect and inhibits cell proliferation. Base on our findings, HA in combination with 50μM of pravastatin (H50P) appear to have the greatest therapeutics effects. It had shown to have suppress NF-κB activity,reduce NO production, and attenuate IL-1β, TNF-α, IL-6, iNOS, caspase 3, MMP-1, andMP-13mRNA expression. Therefore, we suggest that intra articular injection of HA in combination with statin may be feasible for relieve symptoms of knee osteoarthritis.