title: Effect of methylprednisolone and mechanical loading on canine articular cartilage in explant culture.
abstract: The objective of this study was to assess the effect of mechanical load on articular cartilage after in vitro corticosteroid exposure. Canine humeral cartilage was equilibrated for 4 days in defined medium with a serum substitute, then exposed to methylprednisolone sodium succinate for 20 h at 0, 0.01 or 1.0 mg/ml. After a drug-free recovery period, the explants were subjected to 0, 1 or 10 mega pascals (MPa) for 1 out every 5 s for 20 min, then incubated with [35S]-sulfate and [3H]-leucine for 4 h to measure proteoglycan and protein synthesis, respectively. When the loading occurred 22 h after drug exposure, proteoglycan synthesis was inhibited and protein synthesis, was unaffected by the drug. Both were stimulated by load, relative to controls. When the loading was delayed until 142 h after drug exposure, there was no biosynthetic response to load whether or not the explant had been exposed to the drug. Proteoglycan and protein synthesis 142 h after 0 or 0.01 mg/ml were unchanged or slightly higher than at 22 h, in explants which did not receive load. In contrast, biosynthesis were strongly inhibited 142 h after 1.0 mg/ml, and there was a 40% loss of proteoglycan content, relative to 22 h controls. If explants receiving 1.0 mg/ml also received heavy (10 MPa) loads 142 h later, there was a 17% reduction in total dry content suggesting severe matrix damage. These in vitro results suggest that articular load can help maintain normal cartilage metabolism after corticosteroid exposure, but also suggest that heavy loading after a sub-clinical dose can cause a marked loss of matrix solids.
authors.affiliation: Department of Mechanical Engineering, University of Maryland Baltimore County 21228, USA.
authors.forename: T
authors.initials: T
authors.lastname: Farquhar
authors.forename: R J
authors.initials: RJ
authors.lastname: Todhunter
authors.forename: S L
authors.initials: SL
authors.lastname: Fubini
authors.forename: N
authors.initials: N
authors.lastname: Burton-Wurster
authors.forename: G
authors.initials: G
authors.lastname: Lust
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D046508:Culture Techniques; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D006811:Humerus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis; D016474:Weight-Bearing
chemical_list: D005938:Glucocorticoids; D011509:Proteoglycans; D008776:Methylprednisolone Hemisuccinate