Evaluating the Effects of Carnosic acid on TNF-α Gene Expression in LPS-activated Synoviocytes

Abstract

Introduction: Osteoarthritis (OA) is a major cause of disability among adults. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone and inflammation of the synovium tissue and tendon. Non-pharmacologic agents modulating pro-inflammatory mediator expression offer considerable promise as safe and effective treatments for OA. The aim of this study was to evaluate the effects of Carnosic acid (CA) on TNF-α gene expression in synoviocytes. Material & methods: To determine the dose response of CA, synoviocytes (5 × 105 cells/well) were incubated at 5% CO2, 37ºC for 72 h with (1) control media alone or (2) CA at concentrations of 0.01, 0.09, 0.1, 0.9, 1, 9,10and 90 mg/ml. Synoviocytes were treated with LPS (20 ng/ml) for 1h and TNF-α mRNA were measured by both reverse-transcriptase PCR and Real-time PCR. Findings: CA reduced TNF-a, expression in LPS-activated synoviocytes to levels similar to nonactivated control levels. Cells activated with 20 ng/ml LPS showed a significant upregulation of TNF-α expression. In activated synoviocytes cells pretreated with CA, TNF-α was reduced by 48/11% when compared to activated control cells. Discussion & conclusions: This study demonstrates that CA acts as a potent inhibitor of TNF-α. Previous research has shown that these mediators are important in the pathogenesis of OA and reduction in these mediators has been associated with amelioration of cartilage breakdown.