And I'm Dean Wang, I'm at UC Irvine in Orange County, California. I'd like to thank my co-authors for this study here. Here are just my disclosures, nothing relevant to this study. So the chondrotoxicity of corticosteroids is pretty well established from prior studies. The basic science literature has shown that there is a dose-dependent chondrotoxicity effect on articular cartilage with both methylprednisolazone, or MP, or triamcinolone, or TA, and that the thresholds for where these steroids are chondrotoxic are above 7 and 18 milligrams, respectively, which are lower than what we typically use clinically, which is 40 milligrams or more. Clinically, this is a randomized controlled trial from JAMA published in 2017 that looked at the effects of injection of triamcinolone versus saline, and what they showed is that patients had a significant loss of cartilage volume on MRI in the steroid-treated group, and they ended this study early because of this observation. However, the effect of corticosteroids on cartilage mechanics hasn't been studied as much. This is an animal study in an equine model where the investigators injected four doses of methylprednisolone over eight weeks, so repeated injections into the joints of these horses, and what they found is that the MP-exposed joints, the cartilage exhibited decreased compressive modulus, decreased shear modulus, increased permeability, and thinner cartilage. However, we rarely repeatedly inject steroids in the clinical setting in humans, and so the purpose of this study was to investigate the in vitro effects of a single one-hour MP or TA exposure on the viability, biochemical content, and mechanics of native articular cartilage explants. Our hypothesis was that a single one-hour steroid exposure would lead to decreases in GAG and collagen content, which would then correspond to decreases in the mechanical properties of cartilage explants. We used juvenile bovine knees where we harvested explants from the femoral condyles of these knees after slaughter, and we had three experimental groups. The first one was a control where we just bathed it in chondrogenic medium. The first experimental group was the MP group where we used 40 milligrams per milliliter, and then the second experimental group was use of triamcinolone, again 40 milligrams per milliliter, and then we exposed them with a dosage that was calculated based on a standard clinical one cc bolus injection into an adult knee while accounting for approximately seven cc's of synovial joint fluid. The explants were exposed for one hour, followed by a thorough wash with chondrogenic medium. They were stored overnight in the incubator, and then testing began at T equals 24 hours after exposure. Our methods, our viability was measured using the live dead assay, our mechanics were measured using the creep indentation testing and tensile testing, and then the extracellular matrix quantity and organization were measured with quantitative biochemistry, specifically looking at GAG and collagen histology to look at GAG and collagen organization, and then we also used mass spectrometry to look at paradinoline content, which measures a degree of collagen cross-linking. So first, our results, our viability, what we found was that there was a significant decrease in chondrocyte viability in MP-exposed explants. We did not find a similar effect with the TA-exposed explants. So the control group, as you notice, is about 50% viability here, which is not ideal, but we think that this is because of the use of juvenile bovine explants, which are much more cellular and may be more susceptible to stresses from in vitro culture. With our biochemistry results, we did not find any difference in GAG or collagen content or organization between groups, contrary to our hypothesis. We did see a small decrease in paradinoline content in the TA-exposed explants, as shown on the bar graph on the far right there. But overall, no difference in GAG and collagen content or organization. However, we did see a decrease in compressive and tensile mechanical property change in both the MP and TA-exposed explants. The tensile mechanical properties, we found an effect with the UTS, where the MP and TA-exposed groups were much lower than control. And then with the compressive mechanical property assessment, we found decreases in the shear modulus and aggregate modulus for both steroid-exposed groups. So in conclusion, a single one-hour exposure of methylprenisolone produced chondrotoxic effects on native articular cartilage explants. A single one-hour exposure of methylprenisolone or triamcinolone was correlated with decreases in the tensile and compressive properties of native articular cartilage explants. The clinical concern here is that these changes, even though they're transient, may predispose the cartilage tissue to mechanical failure. Therefore, clinicians should be judicious regarding the use of intraarticular corticosteroids, particularly in patients with intact, healthy articular cartilage. Thank you. �

chondrotoxicity

corticosteroids

articular cartilage

viability

mechanical properties