Evidence map›Paper›PMID 33273561›Full record

ArticleScientific reports2020

Distinct roles for the hypoxia-inducible transcription factors HIF-1α and HIF-2α in human osteoclast formation and function.

Helen J Knowles

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. The Interplay of Angiogenesis and Osteogenesis in Non-Stabilized Incomplete Tibial Fractures: A Temporal Study in Rats.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025
    Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. The Bioactive Compounds ofPharmaceuticals (Basel, Switzerland) · 2024
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.International journal of molecular sciences · 2022
    Review
  20. 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

1 author at 1 institution in 1 country.

Helen J KnowlesBotnar Research Centre, Nuffield Department of Orthopaedics Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK. helen.knowles@ndorms.ox.ac.uk.
Nuffield Orthopaedic Centre · GB

Funding

Arthritis Research UK MP/19200Department of HealthVersus Arthritis 19200
6 · The paper itself

Abstract

Bone homeostasis is maintained by a balance between osteoblast-mediated bone formation and osteoclast-driven bone resorption. Hypoxia modulates this relationship partially via direct and indirect effects of the hypoxia-inducible factor-1 alpha (HIF-1α) transcription factor on osteoclast formation and bone resorption. Little data is available on the role(s) of the HIF-2α isoform of HIF in osteoclast biology. Here we describe induction of HIF-1α and HIF-2α during the differentiation of human CD14+ monocytes into osteoclasts. Knockdown of HIF-1α did not affect osteoclast differentiation but prevented the increase in bone resorption that occurs under hypoxic conditions. HIF-2α knockdown did not affect bone resorption but moderately inhibited osteoclast formation. Growth of osteoclasts in 3D gels reversed the effect of HIF-2α knockdown; HIF-2α siRNA increasing osteoclast formation in 3D. Glycolysis is the main HIF-regulated pathway that drives bone resorption. HIF knockdown only affected glucose uptake and bone resorption in hypoxic conditions. Inhibition of glycolysis with 2-deoxy-D-glucose (2-DG) reduced osteoclast formation and activity under both basal and hypoxic conditions, emphasising the importance of glycolytic metabolism in osteoclast biology. In summary, HIF-1α and HIF-2α play different but overlapping roles in osteoclast biology, highlighting the importance of the HIF pathway as a potential therapeutic target in osteolytic disease.

Indexed as

Basic Helix-Loop-Helix ProteinsCell DifferentiationCell HypoxiaCells, CulturedEndothelial PAS Domain-Containing Protein 1GlucoseGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitLipopolysaccharide ReceptorsMonocytesOsteoclastsBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1GlucoseHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitLipopolysaccharide Receptors

Identifiers

PMID33273561
PMCPMC7713367
OpenAlexW3109604488

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.