title: Potential of Raloxifene in reversing osteoarthritis-like alterations in rat chondrocytes: an in vitro model study.
abstract: 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.
authors: Department of Engineering Sciences, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara 06800, Turkey.
authors: Aysegul
authors: A
authors: Kavas
authors: Seda Tuncay
authors: ST
authors: Cagatay
authors: Sreeparna
authors: S
authors: Banerjee
authors: Dilek
authors: D
authors: Keskin
authors: Aysen
authors: A
authors: Tezcaner
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010003:Osteoarthritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024043:Collagen Type II; D020849:Raloxifene Hydrochloride; D000469:Alkaline Phosphatase; D053148:Caspase 3; D020782:Matrix Metalloproteinases; D001374:Azacitidine
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