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- Author or Editor: Evita Busschers x
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Case Description—A 16-year-old Thoroughbred gelding was examined because of chronic right forelimb lameness.
Clinical Findings—On radiographs of the right front foot, the distal interphalangeal (DIP) joint space was narrow, and osteophytes and periarticular bony proliferation indicative of severe osteoarthritis were seen. Arthrodesis of the right DIP joint was recommended to improve the horse's comfort on the limb.
Treatment and Outcome—The horse was anesthetized, and palmar and dorsal arthroscopic approaches were used to remove as much of the articular cartilage as was accessible. Holes were then drilled through the dorsal aspect of the hoof wall, and 3 transarticular, 5.5-mm cortical screws were placed in lag fashion through these holes across the distal phalanx and into the middle phalanx. Defects in the hoof wall were filled with gentamicin-impregnated polymethyl methacrylate plugs and sealed with cyanoacrylate. Eight months after surgery, fusion of the DIP joint was evident radiographically and the horse was sound at a walk.
Clinical Relevance—Transarticular placement of cortical screws through a dorsal hoof wall approach combined with arthroscopically guided cartilage removal can result in fusion of the DIP joint in horses.
Objective—To determine effects of interleukin (IL)-1β and glucocorticoids on total glycosaminoglycan (GAG) loss and aggrecanase-mediated matrix degradation in equine cartilage.
Sample Population—Cartilage from 24 equine cadavers free of sepsis and musculoskeletal disease.
Procedures—Effects of IL-1β, IL-1β with glucocorticoids (dexamethasone and triamcinolone, 10−6 and 10−7M), and glucocorticoids alone on degradation of equine articular and nasal cartilage explants were assessed by measuring GAG release in media and GAG content in cartilage. Aggrecanase-mediated cleavage within the interglobular domain at Glu373-Ala374 was evaluated via western blot analysis and ELISAs. Steady-state mRNA concentrations of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, and ADAMTS5 were assessed by use of real-time reverse transcriptase PCR assay (cartilage explants) and northern blot analysis (cell culture).
Results—IL-1β increased GAG release and aggrecanase activity (11-fold). The MMP-3, MMP-13, and ADAMTS4 mRNA were upregulated with IL-1β, whereas ADAMTS5 mRNA was increased (13-fold), but significantly less than ADAMTS4 mRNA (27-fold), suggesting a role for both ADAMTS4 and ADAMTS5 in degradation of cytokine-stimulated cartilage. Despite downregulation of MMP-3 and MMP-13 mRNA, glucocorticoids did not alter GAG degradation. A further increase in aggrecanase activity was detected with ELISAs and western blot analysis, whereas ADAMTS4 mRNA was downregulated and ADAMTS5 mRNA was maintained or upregulated.
Conclusions and Clinical Relevance—MMP-3, MMP-13, and ADAMTS4 were regulated differently than ADAMTS5. Glucocorticoids increased aggrecanase activity despite down-regulation of ADAMTS4 mRNA, suggesting a major role of ADAMTS5. Effects of glucocorticoids on aggrecanase activity have important implications in terms of treatment.