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.

Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints

“…Additionally, the microspheres showed a significant decrease in average particle size, which might have contributed to the enhancement of release by increasing the surface/volume ratio of the drug delivery system. Although in vitro release amounts of Ral were very small (∼1 μM), this dose is expected to be effective in cartilage regeneration as reported in our previous study . Hydrophobic drugs such as Ral are released with a slow rate from polymeric matrices.…”

“…Although in vitro release amounts of Ral were very small (∼1 :M), this dose is expected to be effective in cartilage regeneration as reported in our previous study. 28 Hydrophobic drugs such as Ral are released with a slow rate from polymeric matrices. Initially, we aimed to enhance Ral release by using coloading with a more hydrophilic drug that would initially open the pores for water penetration into the system.…”

Addressing the Gaps: Therapeutic and Prognostic Considerations in Temporomandibular Joint Osteoarthrosis

“…The other therapies were also tried in the management [24,25]such as lubricin, raloxifen, antioxidants, cathepsins, NGF antibodies, strontium ranelate and various growth factors. Because of the heterogeneity in study design, data collection and data presentation, I did not pool summary data in a metaanalysis.…”

Are estrogen-related drugs new alternatives for the management of osteoarthritis?

“…The consistent effect of SERMs in vivo indicates a protective effect on chondrocytes. Kavas et al [ 53 ] reported that 1 μM of raloxifene reduced expression of OA-related genes, apoptosis, and extracellular matrix-degrading enzymes, and increased extracellular matrix deposition and improved mechanical properties in rat articular chondrocytes with OA-like degeneration. However, these effects were reversed with increased dose, demonstrating that low-dose raloxifene has the potential to cease or decrease cartilage degeneration in OA.…”