Prediction of antiarthritic drug efficacies by monitoring active matrix metalloproteinase-3 (MMP-3) levels in collagen-induced arthritic mice using the MMP-3 probe

Aeju Lee, Kyeongsoon Park, Sungjae Choi, Dong Hyun Seo, Kwang Meyung Kim, Han Sung Kim, Kuiwon Choi, Ick Chan Kwon, Soo-Young Yoon, Inchan Youn

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.

Original languageEnglish
Pages (from-to)1450-1458
Number of pages9
JournalMolecular Pharmaceutics
Volume11
Issue number5
DOIs
Publication statusPublished - 2014 May 5

Fingerprint

Matrix Metalloproteinase 3
Experimental Arthritis
Drug Monitoring
Pharmaceutical Preparations
Rheumatoid Arthritis
Fluorescence
X-Ray Microtomography
Arthritis
Histology
Down-Regulation
Joints
Serum
Therapeutics
Messenger RNA
Drug Discovery
Knee Joint
Methotrexate
Bone Density
Cartilage
Proteins

Keywords

  • active MMP-3
  • infliximab
  • methotrexate
  • rheumatoid arthritis
  • therapeutic response monitoring

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

Cite this

Prediction of antiarthritic drug efficacies by monitoring active matrix metalloproteinase-3 (MMP-3) levels in collagen-induced arthritic mice using the MMP-3 probe. / Lee, Aeju; Park, Kyeongsoon; Choi, Sungjae; Seo, Dong Hyun; Kim, Kwang Meyung; Kim, Han Sung; Choi, Kuiwon; Kwon, Ick Chan; Yoon, Soo-Young; Youn, Inchan.

In: Molecular Pharmaceutics, Vol. 11, No. 5, 05.05.2014, p. 1450-1458.

Research output: Contribution to journalArticle

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abstract = "Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.",
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