PMID- 24641725
OWN - NLM
STAT- MEDLINE
DCOM- 20141031
LR  - 20211021
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 15
DP  - 2014 Mar 19
TI  - The active form of MMP-3 is a marker of synovial inflammation and cartilage 
      turnover in inflammatory joint diseases.
PG  - 93
LID - 10.1186/1471-2474-15-93 [doi]
AB  - BACKGROUND: Matrix metalloproteinase-3 (MMP-3) plays an important role in the 
      pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). 
      Measurement of active MMP-3 in clinical samples could provide information about 
      progression of rheumatoid diseases, and potentially response to treatment. Hence, 
      we aimed to develop a sensitive assay specifically measuring the active form of 
      MMP-3 (act-MMP-3) both in ex vivo models and in human sera. METHODS: A monoclonal 
      antibody against the first 6 amino acids of act-MMP-3 was developed, and the 
      specificity was carefully tested by comparing total and active MMP-3. A 
      technically robust act-MMP-3 ELISA was produced. For biological validation, human 
      synovial membrane and human cartilage explant (HEX) culture models were measured 
      and compared by ELISA and immunoblots. For clinical relevance, the serum levels 
      of act-MMP-3 in AS and RA patients before and after anti-TNF-alpha treatment were 
      evaluated. RESULTS: A highly specific and technically robust ELISA detecting 
      act-MMP-3 in serum was developed. The lower limit of detection was 33.7 pg/mL. 
      The dilution and spiking recovery of human serum was within 100 +/- 20%. The 
      average intra- and inter-assay variations were 3.1% and 13.5% respectively.High 
      levels of act-MMP-3 expression were observed in human synovial membrane culture 
      and oncostatin M and TNF-alpha stimulated human cartilage. In a cross-sectional study 
      of both AS and RA patients, serum act-MMP-3 level was correlated with C-reactive 
      protein (CRP) and erythrocyte sedimentation rate (ESR). In addition, in patients 
      receiving anti-TNF-alpha treatment, the serum level of act-MMP-3 was significantly 
      reduced compared to baseline level reflecting the anti-inflammatory effects of 
      the treatment. CONCLUSION: We have successfully developed an assay measuring 
      act-MMP-3 in human serum showing correlation to inflammatory markers. Further 
      studies are required to clarify, whether act-MMP-3 can serve as a predictive 
      marker for outcome in chronic rheumatoid disorders.
FAU - Sun, Shu
AU  - Sun S
AD  - Nordic Bioscience Biomarkers and Research, Herlev, Denmark. 
      ssu@nordicbioscience.com.
FAU - Bay-Jensen, Anne-Christine
AU  - Bay-Jensen AC
FAU - Karsdal, Morten A
AU  - Karsdal MA
FAU - Siebuhr, Anne Sofie
AU  - Siebuhr AS
FAU - Zheng, Qinlong
AU  - Zheng Q
FAU - Maksymowych, Walter P
AU  - Maksymowych WP
FAU - Christiansen, Thorbjorn G
AU  - Christiansen TG
FAU - Henriksen, Kim
AU  - Henriksen K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140319
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 106956-32-5 (Oncostatin M)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/immunology
MH  - Antirheumatic Agents/therapeutic use
MH  - Arthritis, Rheumatoid/*blood/drug therapy/enzymology
MH  - Biomarkers
MH  - C-Reactive Protein/analysis
MH  - Cartilage/drug effects/*enzymology/metabolism
MH  - Enzyme Activation
MH  - *Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Inflammation
MH  - Male
MH  - Matrix Metalloproteinase 3/*blood/immunology/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oncostatin M/pharmacology
MH  - Organ Culture Techniques
MH  - Osteoarthritis, Knee/pathology
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Specific Pathogen-Free Organisms
MH  - Spondylitis, Ankylosing/*blood/drug therapy/enzymology
MH  - Synovial Membrane/drug effects/*enzymology/metabolism
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/pharmacology
PMC - PMC4003863
EDAT- 2014/03/20 06:00
MHDA- 2014/11/02 06:00
PMCR- 2014/03/19
CRDT- 2014/03/20 06:00
PHST- 2013/10/25 00:00 [received]
PHST- 2014/03/13 00:00 [accepted]
PHST- 2014/03/20 06:00 [entrez]
PHST- 2014/03/20 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
PHST- 2014/03/19 00:00 [pmc-release]
AID - 1471-2474-15-93 [pii]
AID - 10.1186/1471-2474-15-93 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2014 Mar 19;15:93. doi: 10.1186/1471-2474-15-93.