OBJECTIVE: The effects of methotrexate (MTX) on articular cartilage and its influence on the development of osteoarthritis (OA) lesions were tested in a lapine partial medial meniscectomy model. METHOD: Animals were divided into groups consisting of unoperated and operated rabbits that either received or did not receive MTX treatment. After 8 weeks knee articular condylar cartilage was examined for gross and histologic anatomy, active and total neutral metalloproteinases, tissue inhibitor of metalloproteinase (TIMP), DNA, uronic acid and hydroxyproline content. RESULTS: Carbon black retention and histologic scores revealed moderately severe changes in the OA animals with a tendency to less severe changes in OA animals receiving MTX. Unoperated animals receiving MTX had abnormal cartilage that displayed pitting and elevations in histologic score. Active and total neutral metalloproteinase and TIMP were elevated in both untreated and treated OA animals when compared to either unoperated or unoperated and treated animals. CONCLUSION: Articular cartilage with lesser amounts of neutral metalloproteinase and high amounts of TIMP levels often seen with other therapeutic modalities for OA, were not observed with MTX therapy. Our data suggest that MTX may have limited value in the treatment of OA.
OBJECTIVE: The effects of methotrexate (MTX) on articular cartilage and its influence on the development of osteoarthritis (OA) lesions were tested in a lapine partial medial meniscectomy model. METHOD: Animals were divided into groups consisting of unoperated and operated rabbits that either received or did not receive MTX treatment. After 8 weeks knee articular condylar cartilage was examined for gross and histologic anatomy, active and total neutral metalloproteinases, tissue inhibitor of metalloproteinase (TIMP), DNA, uronic acid and hydroxyproline content. RESULTS: Carbon black retention and histologic scores revealed moderately severe changes in the OA animals with a tendency to less severe changes in OA animals receiving MTX. Unoperated animals receiving MTX had abnormal cartilage that displayed pitting and elevations in histologic score. Active and total neutral metalloproteinase and TIMP were elevated in both untreated and treated OA animals when compared to either unoperated or unoperated and treated animals. CONCLUSION:Articular cartilage with lesser amounts of neutral metalloproteinase and high amounts of TIMP levels often seen with other therapeutic modalities for OA, were not observed with MTX therapy. Our data suggest that MTX may have limited value in the treatment of OA.
Authors: Sarah R Kingsbury; Puvan Tharmanathan; Nigel K Arden; Michael Batley; Fraser Birrell; Kim Cocks; Michael Doherty; Chris J Edwards; Toby Garrood; Andrew J Grainger; Michael Green; Catherine Hewitt; Rod Hughes; Robert Moots; Terence W O'Neill; Edward Roddy; David L Scott; Fiona E Watt; David J Torgerson; Philip G Conaghan Journal: Trials Date: 2015-03-04 Impact factor: 2.279