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In vivo imaging of matrix metalloprotease 12 and matrix metalloprotease 13 activities in the mouse model of collagen-induced arthritis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Ngee Han Lim
  • Ernst Meinjohanns
  • George Bou-Gharios
  • Luke L. Gompels
  • Elisa Nuti
  • Armando Rossello
  • Laurent Devel
  • Vincent Dive
  • Meldal, Morten Peter
  • Hideaki Nagase
Objective. To develop enzyme activatable Förster resonance energy transfer (FRET) substrate probes to detect MMP-12 and MMP-13 activities in vivo in mouse models of inflammatory arthritis Methods. Peptidic FRET probes activated by MMP-12 and MMP-13 were reverse designed from inhibitors selected from a peptide phosphinic inhibitor library. Selectivity of the probes was demonstrated in vitro using MMP-1, MMP-2, MMP-3, MMP-12, and MMP-13. In vivo activation of the probe was tested in the zymosan-induced mouse model of inflammation and probe specificity was evaluated by the metalloprotease inhibitor GM6001 and specific synthetic inhibitors of MMP-12 and MMP-13. The probes were used to follow these enzyme activities in the collagen-induced arthritis (CIA) model in vivo. Results. The MMP-12- and MMP-13-activity probes (MMP12ap and MMP13ap, respectively) discriminated between the two enzymatic activities. The in vivo activation of these probes was inhibited by GM6001 and by their respective specific inhibitors. In the CIA model, MMP12ap activation peaked 5 days after disease onset and showed strong correlation with disease severity during this time (r = 0.85; p
OriginalsprogEngelsk
TidsskriftArthritis & Rheumatism
Vol/bind66
Udgave nummer3
Sider (fra-til)589-598
Antal sider10
ISSN0004-3591
DOI
StatusUdgivet - 2014

ID: 99351347