Evidence map›Paper›PMID 34768786›Full record

ArticleInternational journal of molecular sciences2021

Activation of Hypoxia-Inducible Factor-1α Signaling Pathway Has the Protective Effect of Intervertebral Disc Degeneration.

Jin-Woo Kim, Hyun-Ju An, HyunJeong Yeo, Yunhui Jeong, HyeonHae Lee, Jusung Lee, Kisik Nam, Jongheon Lee, Dong-Eun Shin, Soonchul Lee

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
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  12. The NFATc1/P2X7 receptor relationship in human intervertebral disc cells.Frontiers in cell and developmental biology · 2024
    Article
  13. Review
  14. Article
  15. Macrophages and Intervertebral Disc Degeneration.International journal of molecular sciences · 2023
    Review
  16. Review
  17. Concepts of Regeneration for Spinal Diseases in 2022.International journal of molecular sciences · 2022
    Article
  18. 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

10 authors at 2 institutions in 1 country.

Jin-Woo KimDepartment of Orthopaedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul 01830, Korea.ORCID 0000-0003-0186-5834
Hyun-Ju AnDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.ORCID 0000-0002-5359-715X
HyunJeong YeoDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
Yunhui JeongDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
HyeonHae LeeDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
Jusung LeeDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
Kisik NamDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
Jongheon LeeDepartment of Orthopaedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul 01830, Korea.
Dong-Eun ShinDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
Soonchul LeeDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea.
CHA University Bundang Medical Center · KREulji University · KR

Funding

Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, South Korea grant number HI16C1559National Research Foundation of Korea (NRF) grant funded by the Korea government NRF-2019R1C1C1004017National Research Foundation of Korea (NRF) grant funded by the Korea government NRF-2019R1C1C1005658National Research Foundation of Korea (NRF) grant funded by the Korea government NRF-2020R1I1A1A01073917
6 · The paper itself

Abstract

Intervertebral discs (IVDs) have poor nutrient diffusion, because the nucleus pulposus (NP) lacks direct vascular supply and likely generates adenosine triphosphate by anaerobic glycolysis. Regulation of glycolysis is mediated by hypoxia-inducible factor-1α (HIF-1α), a transcription factor that responds to local oxygen tension. Constitutively active HIF-1α (CA HIF-1α) was created by point mutation and determined the protective role of HIF-1α in IVD degeneration. Under fluoroscopy, rat caudal IVD segments were stabbed by a needle puncture, and pcDNA3- HIF-1α wild-type (WT) or pcDNA3-CA HIF-1α was transfected into NP cell lines. The constitutive activity of CA HIF-1α was analyzed using a luciferase assay after cell lysis. Next, IVD tissue samples were retrieved from five patients with degenerative lumbar spinal stenosis at the time of surgery, and NP cells were cultured. NP cells were transfected with CA HIF-1α, and relevant gene expression was measured. HIF-1α protein levels in the nucleus were significantly higher, and transcriptional activity was 10.3-fold higher in NP cells with CA HIF-1α than in those with HIF-1α WT. Gene transfer of CA HIF-1α into NP cells enhanced the expression of Glut-1, Glut-3, aggrecan, type II collagen, and Sox9. Moreover, CA HIF-1α reduced the apoptosis of NP cells induced by the Fas ligand. The HIF-1α and collagen 2 expression levels were notably increased in the NP cells of the CA HIF-1α transfected segments in histology and immunohistochemistry study. Collectively, these results suggest that activation of HIF-1α signaling pathway may play a protective role against IVD degeneration and could be used as a future therapeutic agent.

Indexed as

AnimalsCell LineCollagen Type IIGene ExpressionGene Expression RegulationGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitIntervertebral DiscIntervertebral Disc DegenerationMaleNucleus PulposusRatsRats, Sprague-DawleySignal TransductionCollagen Type IIHIF1A protein, humanHypoxia-Inducible Factor 1, alpha Subunitdegenerationhypoxia inducible factor-1αintervertebral discprotection

Identifiers

PMID34768786
PMCPMC8583205
OpenAlexW3207879068

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.