title: Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3-specific polymeric probe.
abstract: OBJECTIVE
  Early treatment based on an early diagnosis of rheumatoid arthritis (RA) could halt progression of the disease, but early diagnosis is often difficult. Matrix metalloproteinase 3 (MMP-3) is thought to be particularly important in the pathogenesis of RA. The aim of this study was to investigate whether an MMP-3-specific polymeric probe could be used for early diagnosis and for visualizing the progression of arthritis, using a near-infrared fluorescence (NIRF) imaging system.
  
  
  METHODS
  The MMP-3-specific polymeric probe was developed by conjugating NIRF dye, MMP substrate peptide, and dark quencher to self-assembled chitosan nanoparticles. One hour after intravenous administration of the probe, fluorescent images of mice with collagen-induced arthritis at different stages of disease development were obtained. The correlation between the fluorescence recovered in in vivo imaging when using an MMP-3-specific polymeric probe and up-regulated MMP-3 activity in the joint tissues was evaluated by Western blotting and immunohistochemical staining. Histologic analysis and micro-computed tomography (micro-CT) were also used to assess arthritis progression.
  
  
  RESULTS
  A significantly higher NIRF signal was recovered from arthritic joints compared with normal joints at 14 days after the first immunization, before any erythema or swelling could be observed with the naked eye or any erosion was detected by histologic analysis or micro-CT. The results of immunohistochemical analysis and Western blotting confirmed that the fluorescence recovered in the in vivo imaging was related to up-regulated MMP-3 activity in the joint tissues.
  
  
  CONCLUSIONS
  An MMP-3-specific polymeric probe provided clear early diagnosis of arthritis and visualization of arthritis progression using an NIRF imaging system. This approach could be used for early diagnosis and for monitoring drug and surgical therapies in individual cases.
authors: Korea Institute of Science and Technology, Seoul, and Seoul National University, Seoul, Republic of Korea.
authors: Ju Hee
authors: JH
authors: Ryu
authors: Aeju
authors: A
authors: Lee
authors: Jun-Uk
authors: JU
authors: Chu
authors: Heebeom
authors: H
authors: Koo
authors: Chang-Yong
authors: CY
authors: Ko
authors: Han Sung
authors: HS
authors: Kim
authors: Soo-Young
authors: SY
authors: Yoon
authors: Byung-Soo
authors: BS
authors: Kim
authors: Kuiwon
authors: K
authors: Choi
authors: Ick Chan
authors: IC
authors: Kwon
authors: Kwangmeyung
authors: K
authors: Kim
authors: Inchan
authors: I
authors: Youn
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D001175:Arthrography; D015415:Biomarkers / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D042241:Early Diagnosis; D005456:Fluorescent Dyes / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D053758:Nanoparticles; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D005456:Fluorescent Dyes; D019278:Matrix Metalloproteinase 3