Evidence map›Paper›PMID 22102413›Full record

Trial reportThe Journal of biological chemistry2012

Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145).

Aida Martinez-Sanchez, Katarzyna A Dudek, Chris L Murphy

Open access · hybridAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
6.9field-weighted citation impact, top 3% 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

95 citing papers in PubMed, 217 citations in OpenAlex.

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35 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 2 countries.

Aida Martinez-SanchezKennedy Institute of Rheumatology, University of Oxford, 65 Aspenlea Road, London W6 8LH, United Kingdom.
Katarzyna A Dudek
Chris L Murphy
University of Oxford · GBKennedy Center · DK

Funding

Biotechnology and Biological Sciences Research Council BB/G006555/1
6 · The paper itself

Abstract

Articular cartilage enables weight bearing and near friction-free movement in the joints. Critical to its function is the production of a specialized, mechanocompetent extracellular matrix controlled by master regulator transcription factor SOX9. Mutations in SOX9 cause campomelic dysplasia, a haploinsufficiency disorder resulting in severe skeletal defects and dwarfism. Although much is understood about how SOX9 regulates cartilage matrix synthesis and hence joint function, how this master regulator is itself regulated remains largely unknown. Here we identify a specific microRNA, miR-145, as a direct regulator of SOX9 in normal healthy human articular chondrocytes. We show that miR-145 directly represses SOX9 expression in human cells through a unique binding site in its 3'-UTR not conserved in mice. Modulation of miR-145 induced profound changes in the human chondrocyte phenotype. Specifically, increased miR-145 levels cause greatly reduced expression of critical cartilage extracellular matrix genes (COL2A1 and aggrecan) and tissue-specific microRNAs (miR-675 and miR-140) and increased levels of the hypertrophic markers RUNX2 and MMP13, characteristic of changes occurring in osteoarthritis. We propose miR-145 as an important regulator of human chondrocyte function and a new target for cartilage repair.

Indexed as

3' Untranslated RegionsAggrecansAnimalsCampomelic DysplasiaCartilage, ArticularCells, CulturedChondrocytesCollagen Type IIGene Expression RegulationHumansMiceMicroRNAsMutationSOX9 Transcription Factor3' Untranslated RegionsAggrecansCOL2A1 protein, humanCollagen Type IIMicroRNAsMIRN145 microRNA, humanMIRN675 microRNA, humanMIRN675 microRNA, mouseSOX9 protein, humanSOX9 Transcription Factor

Identifiers

PMID22102413
PMCPMC3256897
OpenAlexW2089453524

What OpenQuestion holds

Textmetadata
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.