Optimization of matrix metalloproteinase fluorogenic probes for osteoarthritis imaging

Ju Hee Ryu, Aeju Lee, Jin Hee Na, Seulki Lee, Hyung Jun Ahn, Jong Woong Park, Cheol Hee Ahn, Byung Soo Kim, Ick Chan Kwon, Kuiwon Choi, Inchan Youn, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Among the classical collagenases, matrix metalloproteinase-13 (calledMMP-13, collagenase-3) is one of the most important components for cartilage destruction of osteoarthritis (OA) developments. Despite many efforts, the detection methods of MMP-13 activity have been met with limited success in vivo, in part, due to the low sensitivity and low selectivity by homology of MMP family. Previously, we demonstrated the use of strongly dark-quenched fluorogenic probe allowed for the visual detection of MMP- 13 in vitro and in OA-induced rat models. In this study, we described the optimization of MMP-13 fluorogenic probe for OA detection in vivo. Three candidate probes demonstrated recovered fluorescent intensity proportional with MMP-13 concentrations, respectively; however, Probe 2 exhibited both high signal amplification and selective recognition for MMP-13, not MMP-2 and MMP-9 in vitro. When Probe 2 was applied to OA-induced rat models, clear visualization of MMP-13 activity in OA-induced cartilage was obtained. Optimized MMP-13 fluorogenic probe can be applied to detect and image OA and have potential for evaluating the in vivo efficacy of MMP-13 inhibitors which are being tested for therapeutic treatment of OA.

Original languageEnglish
Pages (from-to)1113-1122
Number of pages10
JournalAmino Acids
Volume41
Issue number5
DOIs
Publication statusPublished - 2011 Nov

Keywords

  • Fluorogenic probe
  • Matrix metalloproteinase (MMP)
  • Optical imaging
  • Osteoarthritis
  • Peptide

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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