Evidence map›Paper›PMID 27741237›Full record

ArticlePloS one2016

Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

Eon Jeong Nam, Jin Hee Kang, Keum Hee Sa, Shijin Sung, Jae Yong Park, Dong-Gyu Jo, Jae Hyung Park, In San Kim, Young Mo Kang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Inhibition of MMPs and ADAM/ADAMTS.Biochemical pharmacology · 2019
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Eon Jeong NamDivision of Rheumatology, Department of Internal Medicine, Kyungpook National University, School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, South Korea.
Jin Hee KangDivision of Rheumatology, Department of Internal Medicine, Kyungpook National University, School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, South Korea.
Keum Hee SaDivision of Rheumatology, Department of Internal Medicine, Kyungpook National University, School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, South Korea.
Shijin SungDivision of Rheumatology, Department of Internal Medicine, Kyungpook National University, School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, South Korea.
Jae Yong ParkCell and Matrix Research Institute, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, South Korea.
Dong-Gyu JoSchool of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangangu, Suwon 16419, Republic of Korea.
Jae Hyung ParkDepartment of Polymer Science and Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangangu, Suwon 16419, Republic of Korea.
In San KimBiomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongukgu, Seoul 02792, Republic of Korea.
Young Mo KangDivision of Rheumatology, Department of Internal Medicine, Kyungpook National University, School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, South Korea.
Kyungpook National University · KRKorea Institute of Science and Technology · KRSungkyunkwan University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTherapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis.

methodsWe designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA) model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages.

resultsMFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo.

conclusionThe present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for chronic inflammatory arthritis, thus providing reliable evidence for a MMP-2-cleavable mechanism as a tissue-targeted strategy for treatment of RA.

Indexed as

Amino Acid SequenceAnimalsArthritis, ExperimentalbetaIG-H3 ProteinCell AdhesionCell MovementChemokine CCL2Chronic DiseaseDown-RegulationExtracellular Matrix ProteinsMaleMatrix Metalloproteinase 2MiceMice, Inbred DBAMicroscopy, FluorescenceMolecular Sequence DatabetaIG-H3 ProteinChemokine CCL2Extracellular Matrix ProteinsMatrix Metalloproteinase 2MFK902 peptideRANK LigandRecombinant Fusion ProteinsRecombinant ProteinsRNA, MessengerTransforming Growth Factor betaVascular Cell Adhesion Molecule-1

Identifiers

PMID27741237
PMCPMC5065154
OpenAlexW2530701775

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.