Evidence map›Paper›PMID 34739320›Full record

ArticleScience advances2021

High-impact

Marcella van Hoolwerff, Alejandro Rodríguez Ruiz, Marga Bouma, H Eka D Suchiman, Roman I Koning, Carolina R Jost, Aat A Mulder, Christian Freund, Farshid Guilak, Yolande F M Ramos and 1 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Mutations in fibronectin dysregulate chondrogenesis in skeletal dysplasia.Cellular and molecular life sciences : CMLS · 2024
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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 2 institutions in 2 countries.

Marcella van HoolwerffDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0002-7824-9864
Alejandro Rodríguez RuizDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0002-8590-7693
Marga BoumaLUMC hiPSC Hotel, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0002-7422-9583
H Eka D SuchimanDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0002-7168-5516
Roman I KoningSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0001-6736-7147
Carolina R JostSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0001-8342-1094
Aat A MulderSection Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0002-4779-099X
Christian FreundLUMC hiPSC Hotel, Leiden University Medical Center, Leiden, Netherlands.
Farshid GuilakDepartment of Orthopedic Surgery, Washington University and Shriners Hospitals for Children, St. Louis, MO, USA.ORCID 0000-0001-7380-0330
Yolande F M RamosDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0003-1459-413X
Ingrid MeulenbeltDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.ORCID 0000-0001-7786-7081
Leiden University Medical Center · NLShriners Hospitals for Children - St. Louis · US

Funding

VISCOELASTIC PROPERTIES OF NORMAL AND OA CHONDRONSR01AG015768 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 1998 to 2022
$7.7M
NIA NIH HHS R01 AG015768
6 · The paper itself

Abstract

Osteoarthritis is the most prevalent joint disease worldwide, yet progress in development of effective disease-modifying treatments is slow because of lack of insight into the underlying disease pathways. Therefore, we aimed to identify the causal pathogenic mutation in an early-onset osteoarthritis family, followed by functional studies in human induced pluripotent stem cells (hiPSCs) in an in vitro organoid cartilage model. We demonstrated that the identified causal missense mutation in the gelatin-binding domain of the extracellular matrix protein fibronectin resulted in significant decreased binding capacity to collagen type II. Further analyses of formed hiPSC-derived neo-cartilage tissue highlighted that mutated fibronectin affected chondrogenic capacity and propensity to a procatabolic osteoarthritic state. Together, we demonstrate that binding of fibronectin to collagen type II is crucial for fibronectin downstream gene expression of chondrocytes. We advocate that effective treatment development should focus on restoring or maintaining proper binding between fibronectin and collagen type II.

Identifiers

PMID34739320
PMCPMC8570604
OpenAlexW3209372919

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.