Evidence map›Paper›PMID 39021299›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

A Damaging COL6A3 Variant Alters the MIR31HG-Regulated Response of Chondrocytes in Neocartilage Organoids to Hyperphysiologic Mechanical Loading.

Niek Gc Bloks, Zainab Harissa, Giorgia Mazzini, Shaunak S Adkar, Amanda R Dicks, Ghazaleh Hajmousa, Nancy Steward, Roman I Koning, Aat Mulder, Berend B R de Koning and 5 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Article
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  6. Article
  7. Osteoarthritis as a systemic disease.Nature reviews. Rheumatology · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
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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

15 authors.

Niek Gc BloksLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.ORCID 0000-0003-4185-3950
Zainab HarissaWashington University, Saint Louis, MO, 63110, USA.
Giorgia MazziniLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Shaunak S AdkarWashington University, Saint Louis, MO, 63110, USA.
Amanda R DicksWashington University, Saint Louis, MO, 63110, USA.
Ghazaleh HajmousaLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Nancy StewardWashington University, Saint Louis, MO, 63110, USA.
Roman I KoningLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Aat MulderLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Berend B R de KoningLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Margreet KloppenburgLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Rodrigo Coutinho de AlmeidaLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Yolande Fm RamosLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.
Farshid GuilakWashington University, Saint Louis, MO, 63110, USA.
Ingrid MeulenbeltLeiden University Medical Center, Leiden, 2333 ZC, The Netherlands.ORCID 0000-0001-7786-7081

Funding

VISCOELASTIC PROPERTIES OF NORMAL AND OA CHONDRONSR01AG015768 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 1998 to 2022
$7.7M
Washington University Rheumatic DiseasesResearch Resource-based CenterP30AR073752 · NIAMS · WASHINGTON UNIVERSITY · PI Christine T. Pham · 2018 to 2026
$7.6M
Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI MATTHEW J SILVA · 2019 to 2026
$6.8M
Genetically-engineered stem cells for self-regulating arthritis therapyR01AR080902 · NIAMS · WASHINGTON UNIVERSITY · PI Farshid Guilak, Christine T. Pham · 2022 to 2026
$3.7M
OBESITY, BIOMECHANICS, AND INFLAMMATION IN OSTEOARTHRITISR01AG046927 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 2013 to 2023
$3.2M
Deconstructing Cartilage Mechanotransduction by Piezo ChannelsR01AR072999 · NIAMS · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 2020 to 2024
$2.9M
Biobanking and BioMolecular resources Research Infrastructure the Netherlands CP2013-84Dutch Arthritis SocietyDutch Scientific Research council NWO/ZonMW VICI scheme 91816631/528Leiden University Medical CenterNetherlands Organisation of Scientific ResearchNIAMS NIH HHS P30 AR073752NIAMS NIH HHS P30 AR074992NIAMS NIH HHS R01 AR072999NIAMS NIH HHS R01 AR080902NIA NIH HHS R01 AG015768NIA NIH HHS R01 AG046927NIH HHS AG15768NIH HHS AG46927NIH HHS AR072999NIH HHS AR073752NIH HHS AR074992NIH HHS AR080902Pfizer GrotonShriners Hospitals for ChildrenThe data is generated within the scope of the Medical Delta programs Regenerative Medicine 4D: Generating complex tissues with stem cells and printing technology and Improving Mobility with Technology.This publication is part of the LoaD project of the NWA-research program Research by Consortia (ORC) that is financed by the Netherlands Organisation of Scientific Research (NWO). NWA.1389.20.009
6 · The paper itself

Abstract

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR-Cas9 genome engineering in two established human induced pluripotent stem cell-derived in-vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi-omics (mRNA and lncRNA) approach in interaction with hyper-physiological mechanical loading conditions. The damaging variant in COL6A3 results in significantly lower binding between the PCM proteins COLVI and FN and provokes an osteoarthritic chondrocyte state. By subsequently exposing the neocartilage organoids to hyperphysiological mechanical stress, it is demonstrated that the COL6A3 variant in chondrocytes abolishes the characteristic inflammatory signaling response after mechanical loading with PTGS2, PECAM1, and ADAMTS5, as central genes. Finally, by integrating epigenetic regulation, the lncRNA MIR31HG is identified as key regulator of the characteristic inflammatory signaling response to mechanical loading.

Indexed as

ChondrocytesCollagen Type VIOrganoidsHumansMicroRNAsOsteoarthritisStress, MechanicalCOL6A3 protein, humanCollagen Type VIMicroRNAscollagen type VIcyclooxygenase 2exome sequencingosteoarthritis

Identifiers

PMID39021299
PMCPMC11423154

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Registered trials

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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.