Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3-specific polymeric probe

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, Kwang Meyung Kim, Inchan Youn

Research output: Contribution to journalArticle

43 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)3824-3832
Number of pages9
JournalArthritis and Rheumatism
Volume63
Issue number12
DOIs
Publication statusPublished - 2011 Dec 1

Fingerprint

Matrix Metalloproteinase 3
Experimental Arthritis
Arthritis
Early Diagnosis
Joints
Fluorescence
Optical Imaging
Rheumatoid Arthritis
Western Blotting
Tomography
Chitosan
Erythema
Matrix Metalloproteinases
Fluorescent Dyes
Intravenous Administration
Nanoparticles
Disease Progression
Immunization
Coloring Agents
Staining and Labeling

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3-specific polymeric probe. / Ryu, Ju Hee; Lee, Aeju; Chu, Jun Uk; Koo, Heebeom; Ko, Chang Yong; Kim, Han Sung; Yoon, Soo-Young; Kim, Byung Soo; Choi, Kuiwon; Kwon, Ick Chan; Kim, Kwang Meyung; Youn, Inchan.

In: Arthritis and Rheumatism, Vol. 63, No. 12, 01.12.2011, p. 3824-3832.

Research output: Contribution to journalArticle

Ryu, Ju Hee ; Lee, Aeju ; Chu, Jun Uk ; Koo, Heebeom ; Ko, Chang Yong ; Kim, Han Sung ; Yoon, Soo-Young ; Kim, Byung Soo ; Choi, Kuiwon ; Kwon, Ick Chan ; Kim, Kwang Meyung ; Youn, Inchan. / Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3-specific polymeric probe. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 12. pp. 3824-3832.
@article{6b749f180a2048b28630eb5336d58ef2,
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. 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.",
author = "Ryu, {Ju Hee} and Aeju Lee and Chu, {Jun Uk} and Heebeom Koo and Ko, {Chang Yong} and Kim, {Han Sung} and Soo-Young Yoon and Kim, {Byung Soo} and Kuiwon Choi and Kwon, {Ick Chan} and Kim, {Kwang Meyung} and Inchan Youn",
year = "2011",
month = "12",
day = "1",
doi = "10.1002/art.30628",
language = "English",
volume = "63",
pages = "3824--3832",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "12",

}

TY - JOUR

T1 - Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase 3-specific polymeric probe

AU - Ryu, Ju Hee

AU - Lee, Aeju

AU - Chu, Jun Uk

AU - Koo, Heebeom

AU - Ko, Chang Yong

AU - Kim, Han Sung

AU - Yoon, Soo-Young

AU - Kim, Byung Soo

AU - Choi, Kuiwon

AU - Kwon, Ick Chan

AU - Kim, Kwang Meyung

AU - Youn, Inchan

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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. 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.

AB - 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. 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.

UR - http://www.scopus.com/inward/record.url?scp=82455163735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82455163735&partnerID=8YFLogxK

U2 - 10.1002/art.30628

DO - 10.1002/art.30628

M3 - Article

VL - 63

SP - 3824

EP - 3832

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 12

ER -