Potential of Raloxifene in reversing osteoarthritis-like alterations in rat chondrocytes: An in vitro model study

Journal of biosciences

Aysen Tezcaner1 3 4²  Dilek Keskin²  Aysegul Kavas²  Seda Tuncay Cagatay¹  Sreeparna Banerjee¹ 

[1] Department of Biological Sciences, Middle East Technical University, Ankara 06800, Turkey$$;Department of Engineering Sciences, Middle East Technical University, Ankara 06800, Turkey$$

关键词: Agarose;    cartilage;    chondroprotective;    in vitro models;    osteoarthritis;    Raloxifene;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

The aim of this study was to investigate the effects of Raloxifene (Ral) on degeneration-related changes in osteoarthritis (OA)-like chondrocytes using two- and three-dimensional models. Five-azacytidine (Aza-C) was used to induce OA-like alterations in rat articular chondrocytes and the model was verified at molecular and macrolevels. Chondrocytes were treated with Ral (1, 5 and 10 𝜇M) for 10 days. Caspase-3 activity, gene expressions of aggrecan, collagen II, alkaline phosphatase (ALP), collagen X, matrix metalloproteinases (MMP-13, MMP-3 and MMP-2), and MMP-13, MMP-3 and MMP-2 protein expressions were studied in two-dimensional model. Matrix deposition and mechanical properties of agarose-chondrocyte discs were evaluated in three-dimensional model. One 𝜇M Ral reduced expression of OA-related genes, decreased apoptosis, and MMP-13 and MMP-3 protein expressions. It also increased aggrecan and collagen II gene expressions relative to untreated OA-like chondrocytes. In three-dimensional model, 1 𝜇M Ral treatment resulted in increased collagen deposition and improved mechanical properties, although a significant increase for sGAG was not observed. In summation, 1 𝜇M Ral improved matrix-related activities, whereas dose increment reversed these effects except ALP gene expression and sGAG deposition. These results provide evidence that low-dose Ral has the potential to cease or reduce the matrix degeneration in OA.

【 授权许可】

Unknown