Background: Osteoarthritis (OA) is characterized by progressive destruction of the articular cartilage, and chondrocytes, the only cells in articular cartilage, are in charge of maintaining the homeostasis of articular cartilage via modulating extracellular matrix anabolism and catabolism [1]. Due to the association of the degree of oxidative degeneration of chondrocytes and OA, preventing impaired redox signalling and oxidative death of chondrocyte are suggested as potential targets to relieve OA[2]. In this respect, some photochemicals have been shown to be potential agents for preventing or treating OA due to their antioxidant and anti-inflammatory properties [3].

Objectives: We studied the effects of an antioxidant S-allyl-cysteine (SAC), a major sulphur-containing amino acid compound of garlic[4], on the redox system, and its associations with the proliferation rate and index of human OA chondrocytes(OACs).

Methods: Chondrocytes were isolated from the joint cartilages of OA patients (grade 4, meanage= 66 years, BMI= 29.7 ± 4.4 kg/m²).The alterations in cell proliferation (MTT), adhesion profile (RTCA-iCELLigence System), reactive oxygen species generation (ROS), lipid hydroperoxide levels (LPO), HNE-protein adduct levels (HNE), AGE-protein adduct levels(AGE), 3-nitrotyrosine levels (3-NT),glutathione peroxidase activity (GPx), and inflammatory progenitors ICE/caspase-1 (ELISA) were determined.

Results: SAC increased OAC’s proliferation rate and adhesion profile at relatively low concentrations (1, 10 and 100 nM),but inhibited at higher concentrations (1-100 μM). SAC (1 nM-10 μM) inhibited ROS, LPO and 3-NT, but not HNE- and AGE-modified proteins levels. SAC increased GPx but drastically down regulated ICE/caspase-1, indicating a potential redox regulating and anti-inflammatory effect.

Conclusion: Results suggest that SAC has favourable effects on OA chondrocytes through protecting proliferation capacity and ameliorating redox-mediated inflammatory pathways. Further studies are needed to investigate its therapeutic potential in patients with OA.

References [1] Lepetsos P, Papavassiliou AG. ROS/oxidative stress signalling in osteoarthritis. Biochim Biophys Acta. 2016 Apr;1862(4):576-591.

[2] Drevet S, et al. Reactive oxygen species and NADPH oxidase 4 involvement in osteoarthritis. Exp Gerontol. 2018Oct1;111:107-117.

[3] Goker B, et al. Luteolin Modulates Glyco-Lipo-Oxidative Protein Modifications and Inhibits Inflammatory Cytokine Release in Human Osteoarthritic Articular Chondrocytes: Comparison with Colchicine. 2018 ACR/ARHP Annual Meeting. Abstract Number: 1990.

[4] QianYQ, et al. Down regulating PI3K/Akt/NF-κB signalling with allicin for ameliorating the progression of osteoarthritis: in vitro and vivo studies. Food Funct. 2018Sep19;9(9):4865-4875.

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Figure.

Cell proliferation of human primary chondrocytes (A) and dynamic monitoring of adhesion profile of human primary chondrocytes during SAC (B) treated with SAC (24 h). ICE/caspase-1, ROS, LPO, HNE, AGE, 3-NT levels after SAC (24 h) treatment (C). ap<0.05, bp<0.01, cp<0.001 vs OAC. (Bland-Altman Statistics)

Acknowledgement: Supported by TUBITAK (The Scientific and Technological Research Council of Turkey) Project No: 315S012

Disclosure of Interests: None declared