EFFECTS OF TRIAMCINOLONE ACETONIDE ON EXPRESSION OF GENESINVOLVED IN CELL DEATH BY OXIDATIVE STRESS AND CHONDROCYTE VIABILITY

Abstract

Triamcinolone acetonide (TA) is a glucocorticoids (GCs) used for pain reduction in patients with osteoarthritic (OA) by intra-articular injection. However, how GCs cause toxicity to cartilage are inconclusive. Hypotheses are that GCs induce oxidative stress in chondrocytes and altering expressions of genes involved in cell death and extracellular matrix homeostasis. Therefore, aims of this study are to determine whether TA induces oxidative stress and altered genes involved in cell death and extracellular matrix homeostasis in chondrocytes. Primary chondrocytes isolated from 10 knee OA patients were treated with TA at 0, 1, 5, and 10 mg/ml, with or without 100 µM of vitamin C. For viability analysis, cells were incubated for 7 and 14 days, and for oxidative status and gene expression analyses, cells were incubated for 48 h. Results showed that viability of TA-treated chondrocytes significantly decreased in all concentrations tested. Oxidative stress significantly increased at 5 mg/ml of TA treatment. Addition of vitamin C significantly increases chondrocyte viability and decrease oxidative stress when treated with 5 mg/ml of TA. TA significantly increased expressions of P21, GDF15, cFos, and MMP-3. These results suggest that the causes of TA-induced toxicity to chondrocytes by stimulation of oxidative stress and expressions of genes involving cell death and extracellular matrix degradation. Vitamin C improved cell viability and oxidative status of TA-treated chondrocytes. Knowledge gained from this study will provide information for physicians to improve TA treatment plan in OA patients.