The effects of methotrexate on normal and osteoarthritic lapine articular cartilage.
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.


METHODS
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.


CONCLUSIONS
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.
Mannoni
A
A
Division of Rheumatology, Instituto Ortopedico Toscano, Florence, Italy.
Altman
R D
RD
Muniz
O E
OE
Serni
U
U
Dean
D D
DD
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007719:Knee Joint; D008666:Metalloendopeptidases / Q000378:metabolism; D008727:Methotrexate / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D012016:Reference Values; D019714:Tissue Inhibitor of Metalloproteinases; D014574:Uronic Acids / Q000378:metabolism
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D014574:Uronic Acids; D004247:DNA; D010450:Endopeptidases; D008666:Metalloendopeptidases; D006909:Hydroxyproline; D008727:Methotrexate