Evidence map›Paper›PMID 34425229›Full record

ArticleOsteoarthritis and cartilage2021

Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation.

K Takeuchi, H Ogawa, N Kuramitsu, K Akaike, A Goto, H Aoki, A Lassar, Y Suehara, A Hara, K Matsumoto and 1 more

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

11 authors at 3 institutions in 2 countries.

K TakeuchiDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
H OgawaDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan; Department of Orthopaedic Surgery, Ogaki Tokushukai Hospital, Hayashi-machi 6-85-1, Ogaki, Gifu, 503-0015, Japan. Electronic address: hiroyasu.ogawa@tokushukai.jp.
N KuramitsuDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
K AkaikeDepartment of Orthopaedic Surgery, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8431, Japan.
A GotoDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
H AokiDepartment of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
A LassarDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave., Boston, MA, 02115, USA.
Y SueharaDepartment of Orthopaedic Surgery, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8431, Japan.
A HaraDepartment of Tumor Pathology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
K MatsumotoDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
H AkiyamaDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, Gifu, 501-1194, Japan.
Gifu University · JPJuntendo University · JPHarvard University · US

Funding

Elucidation of the Role of Creb5 in Synovial Joint FormationR01AR074385 · NIAMS · HARVARD MEDICAL SCHOOL · PI LASSAR, ANDREW BRUCE · 2019 to 2024
$3.4M
Identification of the transcriptional regulators of chondrocyte hypertrophyR01AR055552 · NIAMS · HARVARD MEDICAL SCHOOL · PI LASSAR, ANDREW BRUCE · 2010 to 2014
$1.8M
Role of GATA6 in regulating hedgehog signaling in the growth plateR01AR060735 · NIAMS · HARVARD MEDICAL SCHOOL · PI LASSAR, ANDREW BRUCE · 2013 to 2017
$1.8M
Fate mapping and signaling pathways of superficial cells in articular cartilageR21AR055148 · NIAMS · HARVARD MEDICAL SCHOOL · PI LASSAR, ANDREW BRUCE · 2010 to 2011
$412k
NIAMS NIH HHS R01 AR055552NIAMS NIH HHS R01 AR060735NIAMS NIH HHS R01 AR074385NIAMS NIH HHS R21 AR055148
6 · The paper itself

Abstract

objectiveLow molecular weight compounds that reduce the expression of MMP13 at the mRNA level might serve as disease-modifying osteoarthritis (OA) drugs (DMOADs). The objective of this study was to identify a candidate DMOAD that targets MMP13 expression.

designHigh-throughput screening was performed to identify compounds that suppress inflammatory cytokine-induced MMP13 expression. Ingenuity pathway analysis (IPA) using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to identify signaling pathways related to cytokines. MMP13 expression in chondrocytes was evaluated through RT-qPCR and western blotting analyses. Additionally, 10-week-old mice were subjected to destabilization of the medial meniscus (DMM) surgery to induce OA and were sacrificed 12 weeks post-surgery for pathological examination. OA was evaluated using the OARSI scoring system.

resultsColchicine was identified as a DMOAD candidate as it inhibited inflammatory cytokine-induced MMP13 expression in vitro, and the colchicine-administered mice with DMM presented significantly lower OARSI scores (adjusted P: 0.0242, mean difference: 1.6, 95% confidence interval (CI) of difference: 0.1651-3.035) and significantly lower synovial membrane inflammation scores (adjusted P: 0.0243, mean difference: 0.6, 95% CI of difference: 0.06158-1.138) than mice with DMM. IPA further revealed that components of the Rho signaling pathways are regulated by cytokines and colchicine. IL-1β and TNF-α activate RAC1 and SRC signals, respectively, leading to the phosphorylation of PLC-γ1 and synergistic induction of MMP13 expression. Most notably, colchicine abrogates inflammatory cytokine-induced phosphorylation of PLC-γ1, leading to the induction of MMP13 expression.

conclusionsColchicine is a potential DMOAD candidate that inhibits MMP13 expression and consequent cartilage degradation by disrupting the SRC/RAC1-phospho-PLCγ1-Ca

Indexed as

AnimalsChondrocytesColchicineMatrix Metalloproteinase 13MiceMice, Inbred C57BLOsteoarthritisPhospholipase C gammaPhosphorylationRNA, MessengerSignal TransductionSynovial MembraneColchicineMatrix Metalloproteinase 13Phospholipase C gammaRNA, MessengerChondrocyteColchicineDisease-modifying osteoarthritis drugsDrug screeningMatrix metalloproteinase13OsteoarthritisPLC-γ1

Identifiers

PMID34425229
PMCPMC8542595
OpenAlexW3194788191

What Socratic holds

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LicenceTDM
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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 Socratic graph.