MT3-MMP (MMP-16) is downregulated by in vitro cytokine stimulation of cartilage, but unaltered in naturally occurring equine osteoarthritis and osteochondrosis.
Matrix degradation by metalloproteinases is considered a key feature in the loss of articular cartilage seen in many joint diseases. Membrane-type matrix metalloproteinase-3 (MT3-MMP) expression is elevated in human cartilage in end-stage osteoarthritis. We investigated whether MT3-MMP is similarly regulated in cartilage in two naturally occurring arthropathies in vivo and whether proinflammatory cytokines regulate its expression in vitro. MT3-MMP expression was evaluated in cartilage from horses with osteoarthritis and osteochondrosis and compared with age- and site-matched normal cartilage. MT3-MMP also was measured in normal cartilage stimulated with proinflammatory cytokines. MT3-MMP expression was not significantly altered in either osteoarthritis or osteochondrosis cartilage. However, gene expression was significantly downregulated by the addition of recombinant human interleukin-1beta, oncostatin M, or tumor necrosis factor-alpha to normal cartilage explants. The results suggest that MT3-MMP may not have a role in matrix destruction in equine cartilage diseases. Further work is required to characterize its regulation and function.
Garvican
E R
ER
Musculoskeletal Research Group, University of Liverpool, Wirral, United Kingdom. e.garvican@liv.ac.uk
Vaughan-Thomas
A
A
Redmond
C
C
Clegg
P D
PD
D000818:Animals; D002358:Cartilage, Articular / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005109:Extracellular Matrix / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006734:Horse Diseases / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006736:Horses; D053583:Interleukin-1beta / Q000276:immunology / Q000494:pharmacology; D053513:Matrix Metalloproteinase 16 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053683:Oncostatin M / Q000276:immunology / Q000494:pharmacology; D010003:Osteoarthritis / Q000201:enzymology / Q000276:immunology / Q000662:veterinary*; D010007:Osteochondritis / Q000201:enzymology / Q000276:immunology / Q000662:veterinary*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D016207:Cytokines; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D053513:Matrix Metalloproteinase 16