PMID- 24673659
OWN - NLM
STAT- MEDLINE
DCOM- 20141218
LR  - 20151119
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 11
IP  - 5
DP  - 2014 May 5
TI  - Prediction of antiarthritic drug efficacies by monitoring active matrix 
      metalloproteinase-3 (MMP-3) levels in collagen-induced arthritic mice using the 
      MMP-3 probe.
PG  - 1450-8
LID - 10.1021/mp400622q [doi]
AB  - 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.
FAU - Lee, Aeju
AU  - Lee A
AD  - Biomedical Research Center, Korea Institute of Science and Technology , 39-1 
      Hawolgok-Dong, Seongbuk-gu, Seoul 136-791, South Korea.
FAU - Park, Kyeongsoon
AU  - Park K
FAU - Choi, Sung-Jae
AU  - Choi SJ
FAU - Seo, Dong-Hyun
AU  - Seo DH
FAU - Kim, Kwangmeyung
AU  - Kim K
FAU - Kim, Han Sung
AU  - Kim HS
FAU - Choi, Kuiwon
AU  - Choi K
FAU - Kwon, Ick Chan
AU  - Kwon IC
FAU - Yoon, Soo-Young
AU  - Yoon SY
FAU - Youn, Inchan
AU  - Youn I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140414
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Molecular Probes)
RN  - 9007-34-5 (Collagen)
RN  - B72HH48FLU (Infliximab)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Experimental/drug therapy/enzymology
MH  - Arthritis, Rheumatoid/drug therapy/enzymology
MH  - Collagen/*toxicity
MH  - Disease Models, Animal
MH  - Infliximab
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Methotrexate/therapeutic use
MH  - Mice
MH  - Molecular Probes/*metabolism
EDAT- 2014/03/29 06:00
MHDA- 2014/12/19 06:00
CRDT- 2014/03/29 06:00
PHST- 2014/03/29 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2014/12/19 06:00 [medline]
AID - 10.1021/mp400622q [doi]
PST - ppublish
SO  - Mol Pharm. 2014 May 5;11(5):1450-8. doi: 10.1021/mp400622q. Epub 2014 Apr 14.