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VERBASCOSIDE AND HYDROXYTYROSOL DOWNREGULATE STRESS-RELATED PATHWAYS IN HUMAN OSTEOARTHRITIC ARTICULAR CHONDROCYTES

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2018-06-01
Elmazoglu, Z.
Colakoglu, M.
Banerjee, Sreeparna
Bitik, B.
Aktekin, C. N.
Goker, B.
Karasu, C.
Background Osteoarthritis (OA), is a leading cause of joint dysfunction and the disease is characterised by progressive destruction of the articular cartilage.¹ At the molecular level, degeneration of the cartilage is attributed to multifactorial events including oxidative stress, mitochondrial dysfunction, apoptosis and associated changes in inflammatory and catabolic gene expression.² Recent studies have revealed the essential role of plant-derived antioxidants in preventing pathophysiological events observed in joint diseases by modulating redox signalling.³ Objectives Here, we studied whether the polyphenolic compounds verbascoside and hydroxytyrosol exert chondroprotective effects by suppressing oxidative stress pathways and IL-1, IL-1β-converting enzyme (ICE) expression in human OA chondrocytes. Methods Chondrocytes were isolated from the joint cartilages of OA patients (grade 3–4) during total knee arthroplasty with the approval of Kecioren Training and Research Hospital, Clinical Research Ethics Committee (B.10.4.İSM.4.06.68.49), as described previously.⁴ The alterations in cell counts, viability (MTT, NRU), proliferation (RTCA-iCELLigence System), reactive oxygen species (ROS) generation, stress-related signalling proteins and inflammatory progenitors ICE/caspase-1 (ELISA) were determined. Results Cell viability was increased at lower concentrations of hydroxytyrosol in OA chondrocytes (P1, 30th day). On the other hand, verbascoside treated cells did not show any difference in the activity of mitochondrial oxidoreductases by the MTT assay. However, both polyphenols significantly increased proliferation and reduced intracellular ROS generation in OA chondrocytes at lower concentrations. Although verbascoside has no effect on ICE/caspase-1, treatment with hydroxytrosol downregulated ICE/caspase-1, indicating a potential anti-inflammatory effect. Both polyphenols modulated the activation of stress activated signalling pathways via p38 and JNK proteins. Conclusions At low concentrations the antioxidants hydroxytyrosol and verbascoside may have potential chondroprotective effects in OA. References [1] Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta2016Apr;1862(4):576–591. [2] Khan NM, Ahmad I, Haqqi TM. Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis. Free Radic Biol Med. 2018Jan 12:S0891–5849(18)30023–6. [3] Chin KY, Pang KL. Therapeutic Effects of Olive and Its Derivatives on Osteoarthritis: From Bench to Bedside. Nutrients2017Sep 26;9(10):E1060. [4] Naranda J, Gradišnik L, Gorenjak M, Vogrin M, Maver U. Isolation and characterization of human articular chondrocytes from surgical waste after total knee arthroplasty (TKA). Peer J. 2017Mar 21;5:e3079. Acknowledgements Acknowledgement: This study is supported by TUBITAK (The Scientific and Technological Research Council of Turkey) Project No: 315 S012. This study is supported by TUBITAK (The Scientific and Technological Research Council of Turkey) Project No: 315 S012. Disclosure of Interest None declared