Anti-Inflammatory Effects of Hydrophilic and Lipophilic Statins with Hyaluronic Acid Against LPS-Induced Inflammation in Porcine Articular Chondrocytes

The objective of the study is to understand the therapeutic effects of lipophilic (simvastatin) and hydrophilic statins (pravastatin) combined with/without hyaluronic acid for osteoarthritis by an in vitro LPS-induced inflammatory model of articular chondrocytes. HA in combination with different doses of simvastatin or pravastatin were used. Beside cytotoxicity, the influence of statins on NO production, pro-inflammatory cytokine, inflammatory mediators, and NF-B p50 protein were analyzed. Finally, TUNEL assay was performed to detect DNA strand breakage. Two statins were less able to lower NF-B activity when they were administrated along without HA. The gene expression demonstrates that simvastatin and pravastatin had the ability to decrease pro-inflammatory and inflammatory mediator levels. High dose simvastatin with or without HA down regulated inflammatory cytokines, but resulted in higher cytotoxicity. TUNEL assay confirms the regulatory effect of statins with or without HA over the apoptosis of chondrocytes, especially in hydrophilic statins. The significant down-regulation of inflammatory mediators suggests that intra-articular injection of HA in combination with statins might feasibly slow the progress of osteoarthritis. Administration of simvastatin or pravastatin with hyaluronic acid may produce beneficial effects for OA treatment, but with better results when hydrophilic statin was used. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:557-565, 2014.