Evidence map›Paper›PMID 33989379›Full record

ArticleRheumatology (Oxford, England)2022

The role of TNFRSF11B in development of osteoarthritic cartilage.

Alejandro Rodríguez Ruiz, Margo Tuerlings, Ankita Das, Rodrigo Coutinho de Almeida, H Eka D Suchiman, Rob G H H Nelissen, Yolande F M Ramos, Ingrid Meulenbelt

Abstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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

8 authors.

Alejandro Rodríguez RuizDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.
Margo TuerlingsDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.
Ankita DasDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.
Rodrigo Coutinho de AlmeidaDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.ORCID 0000-0001-7966-056X
H Eka D SuchimanDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.ORCID 0000-0002-7168-5516
Rob G H H NelissenDepartment of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
Yolande F M RamosDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.ORCID 0000-0003-1459-413X
Ingrid MeulenbeltDepartment of Biomedical Data Sciences, Section Molecular Epidemiology.ORCID 0000-0001-7786-7081

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesOA is a complex genetic disease with different risk factors contributing to its development. One of the genes, TNFRSF11B, previously identified with gain-of-function mutation in a family with early-onset OA with chondrocalcinosis, is among the highest upregulated genes in lesioned OA cartilage (RAAK-study). Here, we determined the role of TNFRSF11B overexpression in development of OA.

methodsHuman primary articular chondrocytes (9 donors RAAK study) were transduced using lentiviral particles with or without TNFRSF11B. Cells were cultured for 1 week in a 3 D in-vitro chondrogenic model. TNFRSF11B overexpression was confirmed by RT-qPCR, immunohistochemistry and ELISA. Effects of TNFRSF11B overexpression on cartilage matrix deposition, matrix mineralization, and genes highly correlated to TNFRSF11B in RNA-sequencing dataset (r >0.75) were determined by RT-qPCR. Additionally, glycosaminoglycans and collagen deposition were visualized with Alcian blue staining and immunohistochemistry (COL1 and COL2).

resultsOverexpression of TNFRSF11B resulted in strong upregulation of MMP13, COL2A1 and COL1A1. Likewise, mineralization and osteoblast characteristic markers RUNX2, ASPN and OGN showed a consistent increase. Among 30 genes highly correlated to TNFRSF11B, expression of only eight changed significantly, with BMP6 showing the highest increase (9-fold) while expression of RANK and RANKL remained unchanged indicating previously unknown downstream pathways of TNFRSF11B in cartilage.

conclusionResults of our 3D in vitro chondrogenesis model indicate that upregulation of TNFRSF11B in lesioned OA cartilage may act as a direct driving factor for chondrocyte to osteoblast transition observed in OA pathophysiology. This transition does not appear to act via the OPG/RANK/RANKL triad common in bone remodeling.

Indexed as

AgedCartilageCartilage DiseasesCells, CulturedChondrocytesEnzyme-Linked Immunosorbent AssayFemaleHumansOsteoarthritisOsteoprotegerinPolymerase Chain ReactionOsteoprotegerinTNFRSF11B protein, humancartilage hypertrophyCCAL1chondrogenesismatrix mineralizationosteoarthritisTNFRSF11B

Identifiers

PMID33989379
PMCPMC8824428

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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.