Osteoarthritis (OA) is the most prevalent joint degenerative disease leading to irreversible structural and functional changes in the joint and is a major cause of disability and reduced life expectancy in ageing population. Despite the high prevalence of OA, there is no disease modifying drug available for the management of OA. Oxidative stress, a result of an imbalance between the production of reactive oxygen species (ROS) and their clearance by antioxidant defense system, is high in OA cartilage and is a major cause of chronic inflammation. Inflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are highly upregulated in OA joints and induce ROS production and expression of matrix degrading proteases leading to matrix degradation and joint dysfunction. ROS and inflammation are interdependent, each being the target of other and represent ideal target/s for the treatment of OA. Plant polyphenols possess potent antioxidant and anti-inflammatory properties and can inhibit ROS production and inflammation in chondrocytes, cartilage explants and in animal models of OA. The aim of this review is to discuss the chondroprotective effects of polyphenols and modulation of different molecular pathways associated with OA pathogenesis and limitations and future prospects of polyphenols in OA treatment.

There is growing evidence in support of the involvement of inflammatory response in the pathogenesis of osteoarthritis (OA). Harpagoside, one of the bioactive components of Harpagophytum procumbens (Hp), has been shown to possess anti‐inflammatory properties. Here we used an in vitro model of inflammation in OA to investigate the potential of harpagoside to suppress the production of inflammatory cytokines/chemokines such as IL‐6 and matrix degrading proteases. We further investigated the likely targets of harpagoside in primary human OA chondrocytes. OA chondrocytes were pre‐treated with harpagoside before stimulation with IL‐1β. mRNA expression profile of 92 cytokines/chemokines was determined using TaqMan Human Chemokine PCR Array. Expression levels of selected mRNAs were confirmed using TaqMan assays. Protein levels of IL‐6 and MMP‐13 were assayed by ELISA and immunoblotting. Total protein levels and phosphorylation of signaling proteins were determined by immunoblotting. Cellular localization of IL‐6 and c‐Fos was performed by immunofluorescence and confocal microscopy. DNA binding activity of c‐FOS/AP‐1 was determined by ELISA. Harpagoside significantly altered the global chemokine expression profile in IL‐1β‐stimulated OA chondrocytes. Expression of IL‐6 was highly induced by IL‐1β, which was significantly inhibited by pre‐treatment of OA chondrocytes with harpagoside. Harpagoside did not inhibit the IL‐1β‐induced activation of NF‐κB and C/EBPβ transcription factors but suppressed the IL‐1β‐triggered induction, phosphorylation, and DNA binding activity of c‐FOS, one of the main components of AP‐1 transcription factors. Further, harpagoside significantly inhibited the expression of MMP‐13 in OA chondrocytes under pathological conditions. siRNA‐mediated knockdown of IL‐6 resulted in suppressed expression and secretion of MMP‐13 directly linking the role of IL‐6 with MMP‐13 expression. Taken together, the present study suggests that harpagoside exerts a significant anti‐inflammatory effect by inhibiting the inflammatory stimuli mediated by suppressing c‐FOS/AP‐1 activity in OA chondrocytes under pathological conditions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:311–320, 2017.