Evidence map›Paper›PMID 25734788›Full record

ArticlePloS one2015

TNFα transport induced by dynamic loading alters biomechanics of intact intervertebral discs.

Benjamin A Walter, Morakot Likhitpanichkul, Svenja Illien-Junger, Peter J Roughley, Andrew C Hecht, James C Iatridis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. 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
3.1field-weighted citation impact, top 9% 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, 43 citations in OpenAlex.

  1. Review
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  4. CT- and MRI-based endplate osteoporosis status assessment for predicting adjacent vertebral fractures after thoracolumbar percutaneous kyphoplasty: a matched comparison study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025
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  17. PreclinicalFrontiers in bioengineering and biotechnology · 2020
    Article
  18. Article
  19. Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration.The spine journal : official journal of the North American Spine Society · 2018
    Article
  20. Article
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 3 institutions in 2 countries.

Benjamin A WalterLeni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America; Department of Biomedical Engineering, The City College of New York, New York, NY, United States of America.
Morakot LikhitpanichkulLeni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Svenja Illien-JungerLeni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Peter J RoughleyShriners Hospital for Children, Montreal QC, Canada.
Andrew C HechtLeni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
James C IatridisLeni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Icahn School of Medicine at Mount Sinai · USCity College of New York · USShriners Hospitals for Children - Canada · CA

Funding

Model of Human Disc Regeneration in the spectrum of Degenerative Disc DiseaseR01AR057397 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI IATRIDIS, JAMES C. · 2011 to 2021
$5.1M
Notochordal Cell Derived Therapies for Painful Disc DegenerationR01AR064157 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI IATRIDIS, JAMES C. · 2013 to 2017
$2.7M
NIAMS NIH HHS R01 AR057397NIAMS NIH HHS R01AR057397NIAMS NIH HHS R01 AR064157NIAMS NIH HHS R01AR064157
6 · The paper itself

Abstract

objectiveIntervertebral disc (IVD) degeneration is an important contributor to the development of back pain, and a key factor relating pain and degeneration are the presence of pro-inflammatory cytokines and IVD motion. There is surprisingly limited understanding of how mechanics and inflammation interact in the IVD. This study investigated interactions between mechanical loading and pro-inflammatory cytokines in a large animal organ culture model to address fundamental questions regarding (i.) how inflammatory mediators arise within the IVD, (ii.) how long inflammatory mediators persist, and (iii.) how inflammatory mediators influence IVD biomechanics.

methodsBovine caudal IVDs were cultured for 6 or 20-days under static & dynamic loading with or without exogenous TNFα in the culture medium, simulating a consequence of inflammation of the surrounding spinal tissues. TNFα transport within the IVD was assessed via immunohistochemistry. Changes in IVD structural integrity (dimensions, histology & aggrecan degradation), biomechanical behavior (Creep, Recovery & Dynamic stiffness) and pro-inflammatory cytokines in the culture medium (ELISA) were assessed.

resultsTNFα was able to penetrate intact IVDs when subjected to dynamic loading but not static loading. Once transported within the IVD, pro-inflammatory mediators persisted for 4-8 days after TNFα removal. TNFα exposure induced changes in IVD biomechanics (reduced diurnal displacements & increased dynamic stiffness). DISCUSSION: This study demonstrated that exposure to TNFα, as might occur from injured surrounding tissues, can penetrate healthy intact IVDs, induce expression of additional pro-inflammatory cytokines and alter IVD mechanical behavior. We conclude that exposure to pro-inflammatory cytokine may be an initiating event in the progression of IVD degeneration in addition to being a consequence of disease.

Indexed as

Elastic ModulusAnimalsCattleCytokinesEnzyme-Linked Immunosorbent AssayHumansImmunohistochemistryIntervertebral DiscMicroscopy, FluorescenceOrgan Culture TechniquesTumor Necrosis Factor-alphaCytokinesTNF protein, humanTumor Necrosis Factor-alpha

Identifiers

PMID25734788
PMCPMC4348425
OpenAlexW2075157239

What OpenQuestion holds

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LicenceCC BY
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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.