The effects of methylprednisolone on normal and monocyte-conditioned medium-treated articular cartilage from dogs and horses

Objective-To study in vitro (1) the dose-response relationships between pro teoglycan metabolism in normal and corticosteroid-treated articular cartila ge: (2) long-term proteoglycan metabolism after treatment of articular cart ilage with corticosteroids; and (3) the effect of corticosteroids on proteo glycan metabolism in articular cartilage treated with monocyte-conditioned medium (MCM). Study Design-Equine and canine articular cartilage explants were treated wi th corticosteroids and MCM. Proteoglycan synthesis and degradation were mea sured by radioactive labeling in short-term culture, and the long-term effe ct of corticosteroid treatment on proteoglycan metabolism was studied in no rmal explants. Animals-Two young cross-breed horses and 3 young Labrador retrievers. Methods-Equine articular cartilage explants were incubated in medium contai ning methylprednisolone sodium succinate (MPS) at 0, .001, .01, .1, 1, and 10 mg/mL (final concentration) for 1 day and then in fresh medium without M PS. Proteoglycan synthesis was measured by incorporation of sodium [S-35]su lfate at 1, 3, 7, 10, and 13 days after initial treatment with MPS. Proteog lycan release was measured from separate explants prelabeled with sodium [S -35]sulfate and treated similarly. Equine articular cartilage explants were treated with equine MCM simultaneously with, and 24 hours before MPS, at 0 , 0.01, 0.1, 1, or 5 mg/mL for 72 hours. Proteoglycan synthesis and degrada tion in these explants was compared. Proteoglycan synthesis and degradation were measured similarly in canine articular cartilage explants treated sim ultaneously with canine MCM and MPS at 0, 0.001, 0.01, 0.1, 1 and 10 mg/mL for 72 hours. Equine articular cartilage explants treated with 0, 0.01, 0.1 , 1, and 5 mg/mL of NIPS for 72 hours were evaluated histologically. Results-Proteoglycan synthesis in normal equine articular cartilage was sev erely depressed by 10 mg/mL MPS for 24 hours, and proteoglycan synthesis fa iled to recover after 13 days of culture in medium without NIPS. Cartilage treated with 5 mg/mL NIPS had pyknotic chondrocyte nuclei and empty lacunae . Concentrations of 1 and 0.1 mg/mL MPS depressed proteoglycan synthesis in normal equine cartilage explants. For these 2 concentrations, proteoglycan synthesis recovered 2 days after MPS removal and increased significantly ( P <.05) 7 days after treatment with NIPS compared with controls without MPS . Concentrations of 0.001 and 0.01 mg/mL NIPS did not significantly affect proteoglycan synthesis in normal equine cartilage explants. Cumulative prot eoglycan loss over 13 days in culture from normal equine explants treated f or 24 hours with different concentrations of MPS was not significantly diff erent between treatment groups at any time point. MCM significantly depress ed proteoglycan synthesis in both canine and equine articular cartilage exp lants and significantly increased proteoglycan release. These effects were prevented in the canine explants by simultaneous treatment with MPS at 1 an d 0.1 mg/mL, and proteoglycan release induced by MCM in equine articular ca rtilage was inhibited by 1 mg/mL MPS. Conclusions-Concentrations of 1.0 and 0.1 mg/mL MPS alleviated articular ca rtilage degradation in MCM-treated articular cartilage in vitro. These conc entrations of MPS in contact with normal cartilage explants for 24 hours ar e unlikely to be detrimental in the long term to proteoglycan synthesis. Th e response of articular cartilage to MPS was affected by treatment with MCM so that results of experiments with normal articular cartilage explants ma y not reflect results obtained with abnormal cartilage. Clinical Relevance-It may be possible to find an intraarticular concentrati on of corticosteroid that protects articular cartilage against cytokine-ind uced matrix degradation yet not have prolonged or permanent detrimental eff ects on chondrocyte matrix synthesis. (C) Copyright 2000 by The American Co llege of Veterinary Surgeons.