Evidence map›Paper›PMID 25476526›Full record

ArticleThe American journal of pathology2015

Xylosyltransferase-1 expression is refractory to inhibition by the inflammatory cytokines tumor necrosis factor α and IL-1β in nucleus pulposus cells: novel regulation by AP-1, Sp1, and Sp3.

Wei Ye, Jie Zhou, Dessislava Z Markova, Ye Tian, Jun Li, D Greg Anderson, Irving M Shapiro, Makarand V Risbud

Open access · hybridAbstract read
In one paragraph

Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration.Matrix biology : journal of the International Society for Matrix Biology · 2018
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. 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

8 authors at 2 institutions in 2 countries.

Wei YeDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Orthopaedic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
Jie ZhouDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
Dessislava Z MarkovaDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
Ye TianDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Orthopaedic Surgery, Changzheng Hospital of the Second Military Medical University, Shanghai, China.
Jun LiDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Orthopaedic Surgery, Changzheng Hospital of the Second Military Medical University, Shanghai, China.
D Greg AndersonDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
Irving M ShapiroDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
Makarand V RisbudDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: makarand.risbud@jefferson.edu.
Thomas Jefferson University · USGuangzhou Medical University · CN

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Andrew Chapman · 1995 to 2026
$94.8M
Role of HIF-1 in Intervertebral Disc FunctionR01AR055655 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V · 2008 to 2023
$6.1M
Regeneration of Nucleus Pulposus by Tissue EngineeringR01AR050087 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V, SHAPIRO, IRVING M · 2005 to 2013
$3.0M
Disruption of Osmoregulation Promotes Degenerative Disc DiseaseR01AR064733 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V, SHAPIRO, IRVING M · 2014 to 2018
$2.4M
NCI NIH HHS P30 CA056036NIAMS NIH HHS AR050087NIAMS NIH HHS AR055655NIAMS NIH HHS AR064733NIAMS NIH HHS R01 AR050087NIAMS NIH HHS R01 AR055655NIAMS NIH HHS R01 AR064733
6 · The paper itself

Abstract

We investigated whether expression of xylosyltransferase-1 (XT-1), a key enzyme in glycosaminoglycan biosynthesis, is responsive to disk degeneration and to inhibition by the inflammatory cytokines tumor necrosis factor α and IL-1β in nucleus pulposus (NP) cells. Analysis of human NP tissues showed that XT-1 expression is unaffected by degeneration severity; XT-1 and Jun, Fos, and Sp1 mRNA were positively correlated. Cytokines failed to inhibit XT-1 promoter activity and expression. However, cytokines decreased activity of XT-1 promoters containing deletion and mutation of the -730/-723 bp AP-1 motif, prompting us to investigate the role of AP-1 and Sp1/Sp3 in the regulation of XT-1 in healthy NP cells. Overexpression and suppression of AP-1 modulated XT-1 promoter activity. Likewise, treatment with the Sp1 inhibitors WP631 and mithramycin A or cotransfection with the plasmid DN-Sp1 decreased XT-1 promoter activity. Inhibitors of AP-1 and Sp1 and stable knockdown of Sp1 and Sp3 resulted in decreased XT-1 expression in NP cells. Genomic chromatin immunoprecipitation analysis showed AP-1 binding to motifs located at -730/-723 bp and -684/-677 bp and Sp1 binding to -227/-217 bp and -124/-114 bp in XT-1 promoter. These results suggest that XT-1 expression is refractory to the disease process and to inhibition by inflammatory cytokines and that signaling through AP-1, Sp1, and Sp3 is important in the maintenance of XT-1 levels in NP cells.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsBase SequenceCells, CulturedHumansInterleukin-1betaIntervertebral Disc DegenerationPentosyltransferasesRatsResponse ElementsSequence DeletionSp1 Transcription FactorSp3 Transcription FactorSpineTranscription Factor AP-1Tumor Necrosis Factor-alphaIL1B protein, humanIL1B protein, ratInterleukin-1betaPentosyltransferasesSP1 protein, humanSp1 Transcription FactorSP3 protein, humanSp3 protein, ratSp3 Transcription FactorTranscription Factor AP-1Tumor Necrosis Factor-alphaUDP Xylose-Protein Xylosyltransferase

Identifiers

PMID25476526
PMCPMC4305180
OpenAlexW191562174

What OpenQuestion holds

Textmetadata
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.