Evidence map›Paper›PMID 33198759›Full record

ArticlePediatric rheumatology online journal2020

Juvenile idiopathic arthritis fibroblast-like synoviocytes influence chondrocytes to alter BMP antagonist expression demonstrating an interaction between the two prominent cell types involved in endochondral bone formation.

Megan M Simonds, Amanda R Schlefman, Suzanne M McCahan, Kathleen E Sullivan, Carlos D Rose, AnneMarie C Brescia

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric rheumatology online journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.2field-weighted citation impact, top 49% 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

7 citing papers in PubMed, 9 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

6 authors at 4 institutions in 1 country.

Megan M SimondsNemours Biomedical Research, Nemours A.I. duPont Hospital for Children, 1701 Rockland Rd, Wilmington, DE, 19803, USA. msimonds@nemours.org.ORCID http://orcid.org/0000-0002-2685-2645
Amanda R SchlefmanRheumatology, Nemours A.I. duPont Hospital for Children, Wilmington, DE, USA.
Suzanne M McCahanRheumatology, Nemours A.I. duPont Hospital for Children, Wilmington, DE, USA.
Kathleen E SullivanAllergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Carlos D RoseRheumatology, Nemours A.I. duPont Hospital for Children, Wilmington, DE, USA.
AnneMarie C BresciaRheumatology, Nemours A.I. duPont Hospital for Children, Wilmington, DE, USA.
Community Health Systems - Dupont Hospital · USAlfred I. duPont Hospital for Children · USChildren's Hospital of Philadelphia · USJohns Hopkins University · US

Funding

Synovial Biomarkers in Olgoarticular Juvenile Idiopathic ArthritisK23AR066724 · NIAMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI BRESCIA, ANNEMARIE C · 2014 to 2018
$738k
Nancy Taylor Foundation for Chronic Diseases 3205042004NIAMS NIH HHS K23 AR066724NIH HHS 1K23AR066724-01
6 · The paper itself

Abstract

backgroundTo examine critical interactions between juvenile idiopathic arthritis synovial fibroblasts (JFLS) and chondrocytes (Ch), and their role in bony overgrowth seen in patients with juvenile idiopathic arthritis (JIA).

methodsControl (CFLS) and JFLS were cultured in synoviocyte media containing recombinant BMP4. Ch were cultured in either CFLS or JFLS conditioned-media without stimulation. Media supernatants were analyzed by ELISA. RNA from conditioned media experiment was analyzed by ClariomS microarray.

resultsAs expected, genes expressed in untreated JFLS and CFLS cultured in synoviocyte media were similar to each other and this expression differed from untreated Ch cultured in chondrocyte media. JFLS favor BMP ligand gene expression while downregulating TGFβ receptors' expression. Noggin and chordin, antagonists with high affinity for BMP4, are JFLS- but not Ch-preferred regulators of BMP signaling. Compared to Ch, JFLS overexpress collagen X (COLX), a marker of chondrocyte hypertrophy. Exogenous BMP4 causes JFLS to significantly decrease expression of noggin and collagen II (COL2), a marker of chondrocyte proliferation, and causes overexpression of COLX and alkaline-phosphatase (ALP). Chondrocytes cultured in JFLS-conditioned media (Ch-JFLS) express BMP genes and favor chordin protein expression over other antagonists. Ch-JFLS have significantly increased expression of COL2 and significantly decreased expression of COLX.

conclusionsThese data suggest JFLS, in the presence of BMP4, undergo hypertrophy and that JFLS-conditioned media influence chondrocytes to become highly proliferative. To the authors' knowledge, no prior study has shown that JFLS and chondrocytes play a direct role in the bony overgrowth in joints of patients with JIA and that BMPs or regulation of these growth factors influence the interaction between two prominent synovial cell types.

Indexed as

Arthritis, JuvenileBone Morphogenetic Protein 4Carrier ProteinsChondrocytesSynoviocytesCell CommunicationCell DifferentiationCells, CulturedCollagenGene Expression RegulationHumansHyperostosisNoggin ProteinBMP4 protein, humanBone Morphogenetic Protein 4Carrier ProteinsCollagenNoggin ProteinBMP4BMP antagonistsChondrocyteEndochondral boneFibroblastHypertrophyJuvenile idiopathic arthritisProliferationSynoviocyteTGFβ

Identifiers

PMID33198759
PMCPMC7670793
OpenAlexW3098311047

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.