javascript:void(0) Background: Intraarticular glucocorticoids are widely used in equine practice to treat osteoarthritis (OA) due to their potent antiinflammatory effects. Despite their benefits on diseased joints, glucocorticoids have been shown to be deleterious to normal cartilage. Dose response studies are lacking with no clear guidelines for intraarticular dosages of glucocorticoids in horses. Objectives: To evaluate the in vitro effects of different glucocorticoid doses on cartilage matrix parameters and genetic expression of proinflammatory mediators in an inflammatory milieu to move closer to a clinically relevant intraarticular glucocorticoid doses in horses. Study design: In vitro experimental study Methods: Equine articular cartilage explants were cultured for 3 days in the presence or absence of recombinant human interleukin-1 (rhIL-1) and then treated with three different doses of methylprednisolone sodium succinate (MPS) for 48 hours. Cartilage and media were analyzed for proteoglycan (PG) synthesis and content and PG loss and prostaglandin E 2 levels respectively. Gene expression analysis evaluating the effects of rhIL-1 and MPS as well as glucocorticoid only treated cartilage was performed using Northern blots of total RNA probed with equine specific cDNA probes and rtPCR. Results: MPS maintained cartilage GAG levels in rhIL-1 challenged and unchallenged explants and did not induce increased loss of cartilage PG into media. MPS did inhibit PG synthesis and PGE 2 production dose dependently. mRNA expression of equine stromelysin, IL-1, IL-6 and tissue inhibitor of metalloproteinase (TIMP) were upregulated in explants exposed to rhIL-1 and this effect was significantly downregulated by MPS in both cytokine challenged and in normal cartilage. Limitations: This was an in vitro short term dose response study and clinical efficacy was not evaluated. Conclusions: Higher doses of glucocorticoids are required for chondroprotection in an inflamed joint and lower concentrations of a third to one quarter than that used clinically are beneficial without being detrimental to cartilage.