Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3–specific polymeric probe
✍ Scribed by Ju Hee Ryu; Aeju Lee; Jun-Uk Chu; Heebeom Koo; Chang-Yong Ko; Han Sung Kim; Soo-Young Yoon; Byung-Soo Kim; Kuiwon Choi; Ick Chan Kwon; Kwangmeyung Kim; Inchan Youn
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 423 KB
- Volume
- 63
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
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 upregulated MMP-3 activity in the joint tissues.
Conclusion. 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.
Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease that leads to destruction, deformity, and functional loss in affected joints (1). The inflamed synovial tissues of patients with RA are characterized by hyperplasia, increased vascularity, and substantial inflammatory cell infiltration (2). Because erosions develop in many patients with RA during the first 2 years of the disease, early treatment based on an early diagnosis could halt progression of the disease and prevent irreversible disability (3). However, the early diagnosis of RA is often difficult, because no typical radiographic changes or pathognomonic signs can be observed during the initial stages of the disease