Chondrotoxicity induced by intra-articular injection of corticosteroid in human articular cartilage

Abstract

INTRODUCTION: When a corticosteroid is injected into osteoarthritic knees to decrease synovial swelling, joint effusion and pain, the articular cartilage of the injection site is also exposed to the drug simultaneously. The adverse effect of corticosteroids on chondrocyte of the articular cartilage is a concern. Thus, the number of injections is normally restricted to no more than four times a year. This work is mainly focused on the evaluation and comparison of chondrotoxicity of two commonly used corticosteroids : triamcinolone acetate (TA) and dexamethasone disodium phosphate (DE).MATERIALS AND METHODS: Fresh articular chondrocytes from human knees (degenerative osteoarthritis patients) were collected and incubated with various concentrations of TA or DE for 3 days. The cell proliferation rate was investigated with methylthiazoletetrazolium (MTT) assay and the results were compared with that of the control group (culture media and 0.9% saline solution). Distribution of apoptotic and necrotic cells in samples as well as cell cycle were analyzed using fluorescence-activated cell sorting (FACS) . Glycosaminoglycan (GAG) secretion in the study samples was measured photometrically using sulphated GAG assay. All measurements were performed two days after each sample was exposed to the study drugs with and without 10ng/ml of IL-1β. All samples were tested in triplicates and statistical significance was determined using Student’s t-tests with p<0.05 considered significant.RESULTS: The proliferation of chondrocytes was inhibited during three days of exposure in the TA groups with concentrations higher than 31.25 μg/ml (groups TA1 to TA5) (p<0.02). All the DE groups with drug concentrations lower than 500 μg/ml failed to inhibit the proliferation of chondrocytes from day 1 to day 3, whereas 500 μg /ml of DE inhibited the chondrocyte proliferation. Among them, the

group with the highest concentration of DE below 500 μg/ml was 62.5 μg/ml. A significant decrease in GAG secretion was observed in TA4 (62.5 μg/ml) group (p=0.003) while TA7 (3.125 μg/ml) and DE groups did not affect GAG secretion. Apoptosis was not detected in group TA4 which inhibited proliferation of chondrocyte as well as group TA7 which showed normal proliferation of chondrocyte. The proliferation of 10ng/ml IL-1 treated chondrocyte was inhibited significantly in all TA groups (p<0.02) compared to the control group. The GAG secretion of IL-1 treated chondrocyte decreased significantly (p<0.05) in all TA and DE groups compared to the control group. While the contents were increased upon dilution of TA concentration, the peak content in group TA5 decreased again.CONCLUSION: Dexamethasone disodium phosphate could be considered as a safer corticosteroid for frequent repeated intra-articular injection than triamcinolone acetate with regard to chondrotoxicity. A more frequent intra-articular injection of low concentrations of dexamethasone disodium phosphate might be a viable new treatment strategy for osteoarthritic knees.