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

2013-03-01
Kavas, Aysegul
Cagatay, Seda Tuncay
Banerjee, Sreeparna
Keskin, Dilek
Tezcaner, Ayşen
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 mu M) 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 mu M 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 mu M Ral treatment resulted in increased collagen deposition and improved mechanical properties, although a significant increase for sGAG was not observed. In summation, 1 mu M 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.
JOURNAL OF BIOSCIENCES

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Citation Formats
A. Kavas, S. T. Cagatay, S. Banerjee, D. Keskin, and A. Tezcaner, “Potential of Raloxifene in reversing osteoarthritis-like alterations in rat chondrocytes: An in vitro model study,” JOURNAL OF BIOSCIENCES, pp. 135–147, 2013, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/39772.