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


Kavas A., Cagatay S. T. , Banerjee S. , Keskin D. , Tezcaner A.

JOURNAL OF BIOSCIENCES, cilt.38, ss.135-147, 2013 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 38
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1007/s12038-012-9282-7
  • Dergi Adı: JOURNAL OF BIOSCIENCES
  • Sayfa Sayıları: ss.135-147

Özet

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.