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., 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


Flow-induced vibration analysis of constricted artery models with surrounding soft tissue
Salman, Huseyin Enes; Yazıcıoğlu, Yiğit (2017-10-01)
Arterial stenosis is a vascular pathology which leads to serious cardiovascular diseases. Blood flow through a constriction generates sound and vibration due to fluctuating turbulent pressures. Generated vibro-acoustic waves propagate through surrounding soft tissues and reach the skin surface and may provide valuable insight for noninvasive diagnostic purposes. Motivated by the aforementioned phenomena, vibration of constricted arteries is investigated employing computational models. The flow-induced press...
In vitro and in vivo evaluation of doxycycline-chondroitin sulfate/PCLmicrospheres for intraarticular treatment of osteoarthritis
AYDIN, Ozlem; KORKUSUZ, FEZA; KORKUSUZ, PETEK; Tezcaner, Ayşen; BİLGİÇ, ELİF; Yaprakci, Volkan; Keskin, Dilek (2015-08-01)
Osteoarthritis (OA) is a degenerative joint disease, which has no complete treatment with medication yet. Intraarticular hyaluronan (HA) injection can decrease pain and modify the natural course of OA. This study was designed to provide long term delivery of an MMP (matrix-metalloproteinase) inhibitor agent-doxycycline, together with matrix regenerative agent-chondroitin sulfate for treating OA which progress with matrix degenerations. Doxycycline (D) and doxycycline-chondroitin sulfate (D-CS) loaded poly--...
Evaluation of effectiveness of different bioactive agents for treatment of osteoarthritis with in vitro model under dynamic mechanical stimulation
Kavas, Ayşegül; Tezcaner, Ayşen; Department of Engineering Sciences (2007)
Osteoarthritis (OA) is a disease characterized by the progressive degradation of articular cartilage. Current strategies for the disease are mainly towards relieving symptoms. This study was aimed to investigate the therapeutic potentials of Bone Morphogenetic Protein-9 (BMP-9), Raloxifene (Ral) and Pluronic F-68 (PLF-68) with a three-dimensional in vitro OA model. Articular chondrocytes isolated from rats were cultured in growth media and embedded in agarose to obtain agarose-chondrocyte discs. Dynamic hyd...
In Situ, In Vitro and In Vivo evaluation of effectiveness of new treatment approaches involving controlled drug delivery systems in cartilage degenerations
Aydın, Özlem; Keskin, Dilek; Tezcaner, Ayşen; Department of Engineering Sciences (2011)
Osteoarthritis (OA) is a degenerative joint disease which has yet no complete treatment with medication. Doxycycline, a well-known antibiotic, has been shown to prevent matrixmetallopreoteinases-MMPs, indicating potency on OA treatment. However, long term systemic use can cause side effects on other tissues. This study aimed to develop controlled drug delivery systems of doxycycline/doxycycline-chondroitin sulfate (D/D-CS) in the form of PCL microspheres for providing a better and new treatment approach via...
Development and characterization of injectable alginate/sericin/chondroitin sulphate microspheres for cartilage tissue engineering /
Göl, Nil; Keskin, Dilek; Korkusuz, Feza; Department of Biotechnology (2015)
Osteoarthritis (OA) is one of the joint diseases with the highest prevalence worldwide. Eighty percent of the OA patients present limitation in joint movements and 25% cannot perform their daily activities. Due to loss of regenerative potency in OA joints, treatments with drugs and bioactive agents can provide only limited recovery in the damaged cartilage tissue. Current studies and clinical approaches therefore, mostly focus on cell based treatments with hydrogel carriers. The microcarrier systems supply ...
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