Evidence map›Paper›PMID 28587781›Full record

ArticleOsteoarthritis and cartilage2017

Wnt5a induces catabolic signaling and matrix metalloproteinase production in human articular chondrocytes.

G Huang, S Chubinskaya, W Liao, R F Loeser

Open access · bronzeAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
6.2field-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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

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  17. HU308 Mitigates Osteoarthritis by Stimulating Sox9-Related Networks of Carbohydrate Metabolism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
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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

4 authors at 3 institutions in 2 countries.

G HuangThurston Arthritis Research Center, Division of Rheumatology, Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: ghuang@email.unc.edu.
S ChubinskayaDepartment of Pediatrics, Rush University Medical Center, Chicago, IL, USA. Electronic address: Susanna_Chubinskaya@rush.edu.
W LiaoDepartment of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: liaowmsysu@163.com.
R F LoeserThurston Arthritis Research Center, Division of Rheumatology, Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: richard_loeser@med.unc.edu.
University of North Carolina at Chapel Hill · USRush University Medical Center · USSun Yat-sen University · CN

Funding

Integrin Function in CartilageR37AR049003 · NIAMS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LOESER, RICHARD F · 2012 to 2021
$4.1M
NIAMS NIH HHS R37 AR049003
6 · The paper itself

Abstract

objectiveAberrant Wnt signaling may contribute to osteoarthritis (OA) but the Wnt family members involved have not been fully identified. The purpose of this study was to investigate the role of Wnt5a as a potential mediator of cartilage destruction in OA.

designImmunohistochemistry to detect Wnt5a was performed using normal and OA human articular cartilage. Cultured normal human chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus or recombinant Wnt5a protein with or without pretreatment using a panel of signaling inhibitors. Expression of Wnt5a, anabolic genes and catabolic genes were determined by quantitative real-time PCR. Production of Wnt5a protein and matrix metalloproteinases (MMPs) as well as activation of signaling proteins were analyzed by immunoblotting.

resultsWnt5a was present in human articular cartilage with OA changes and its expression and secretion were increased in FN-f stimulated chondrocytes. FN-f stimulated Wnt5a production through the c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) pathways. Wnt5a reduced aggrecan gene expression after 48 h of treatment. Wnt5a seemed to promote MMP1, -3, and -13 expression as well as MMP1 and MMP13 protein production in normal human chondrocytes. Wnt5a inhibitor peptides did not affect FN-f induced MMP production. Wnt5a activated β-catenin independent signaling including calmodulin-dependent protein kinase II (CaMKII), JNK, p38, ERK1/2, p65 and Akt. Inhibition of JNK, p38, ERK, PI-3 kinase and CaMKII by specific signaling inhibitors suppressed Wnt5a mediated MMP1 and MMP13 production.

conclusionsWnt5a is present in human OA cartilage and can promote chondrocyte catabolic activity through non-canonical Wnt signaling, which suggests a potential role in OA.

Indexed as

AdultAgedAggrecansCartilage, ArticularCells, CulturedChondrocytesGene Expression RegulationHumansMatrix MetalloproteinasesMetabolismMiddle AgedOsteoarthritisRecombinant ProteinsWnt-5a ProteinWnt Signaling PathwayYoung AdultAggrecansMatrix MetalloproteinasesRecombinant ProteinsWnt-5a ProteinWNT5A protein, humanCell signalingChondrocyteIntegrinMetalloproteinaseWnt

Identifiers

PMID28587781
PMCPMC5565712
OpenAlexW2620744636

What OpenQuestion holds

Textmetadata
LicenceTDM
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.