Evidence map›Paper›PMID 27334538›Full record

ArticleArthritis research & therapy2016

Inflammatory conditions partly impair the mechanically mediated activation of Smad2/3 signaling in articular cartilage.

Wojciech Madej, Pieter Buma, Peter van der Kraan

Abstract read
In one paragraph

Article in Arthritis research & therapy, 2016. 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

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3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
  2. Article
  3. The combination of resveratrol andBioengineering & translational medicine · 2023
    Article
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  6. Article
  7. Review
  8. Article
  9. Pathophysiological Perspective of Osteoarthritis.Medicina (Kaunas, Lithuania) · 2020
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
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

3 authors.

Wojciech MadejOrthopedic Research Laboratory, Radboud University Medical Center, Geert Grooteplein-Zuid 10, route 547, 6525, GA, Nijmegen, The Netherlands.
Pieter BumaOrthopedic Research Laboratory, Radboud University Medical Center, Geert Grooteplein-Zuid 10, route 547, 6525, GA, Nijmegen, The Netherlands.
Peter van der KraanExperimental Rheumatology, Radboud University Medical Center, Geert Grooteplein 26-28, route 272, 6525, GA, Nijmegen, The Netherlands. Peter.vanderKraan@radboudumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundJoint trauma, which is frequently related with mechanical overloading of articular cartilage, is a well-established risk for osteoarthritis (OA) development. Additionally, reports show that trauma leads to synovial joint inflammation. In consequence, after joint trauma, cartilage is influenced by deleterious excessive loading combined with the catabolic activity of proinflammatory mediators. Since the activation of TGF-β signaling by loading is considered to be a key regulatory pathway for maintaining cartilage homeostasis, we tested the effect of proinflammatory conditions on mechanically mediated activation of TGF-β/Smad2/3P signaling in cartilage.

methodsCartilage explants were subjected to dynamic mechanical compression in the presence of interleukin-1 beta (IL-1β) or osteoarthritic synovium-conditioned medium (OAS-CM). Subsequently, the activation of the Smad2/3P pathway was monitored with QPCR analysis of reporter genes and additionally the expression of receptors activating the Smad2/3P pathway was analyzed. Finally, the ability for mechanically mediated activation of Smad2/3P was tested in human OA cartilage.

resultsIL-1β presence during compression did not impair the upregulation of Smad2/3P reporter genes, however the results were affected by IL-1β-mediated upregulations in unloaded controls. OAS-CM significantly impaired the compression-mediated upregulation of bSmad7 and Tgbfb1. IL-1β suppressed the compression-mediated bAlk5 upregulation where 12 MPa compression applied in the presence of OAS-CM downregulated the bTgfbr2. Mechanically driven upregulation of Smad2/3P reporter genes was present in OA cartilage.

conclusionsProinflammatory conditions partly impair the mechanically mediated activation of the protective TGF-β/Smad2/3P pathway. Additionally, the excessive mechanical compression, applied in the presence of proinflammatory conditions diminishes the expression of the type II TGF-β receptor, a receptor critical for maintenance of articular cartilage.

Indexed as

Signal TransductionAnimalsCartilage, ArticularCattleChondrocytesGene Expression ProfilingHumansInflammationOrgan Culture TechniquesOsteoarthritisPolymerase Chain ReactionSmad ProteinsStress, MechanicalTranscriptomeTransforming Growth Factor betaSmad ProteinsTransforming Growth Factor betaCartilageDynamic mechanical compressionInflammationOsteoarthritisTransforming growth factor beta

Identifiers

PMID27334538
PMCPMC4918093

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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.