Evidence map›Paper›PMID 39603372›Full record

ArticleBone2025

Osteocytic oxygen sensing: Distinct impacts of VHL and HIF-2alpha on bone integrity.

Sarah V Mendoza, Kristina V Wells, Deepa K Murugesh, Nicholas R Hum, Aimy Sebastian, Bria M Gorman, Alice Wong, Benjamin Osipov, Blaine A Christiansen, Gabriela G Loots and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bone, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Regional and Sexual Dimorphism in Murine Skeletal Responses to Osteocytic HIF Pathway Modulation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026
    Article
  5. Review
  6. 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

13 authors.

Sarah V MendozaDepartment of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA, USA.
Kristina V WellsDepartment of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA, USA.
Deepa K MurugeshLawrence Livermore National Laboratories, Livermore, CA, USA.
Nicholas R HumLawrence Livermore National Laboratories, Livermore, CA, USA.
Aimy SebastianLawrence Livermore National Laboratories, Livermore, CA, USA.
Bria M GormanLawrence Livermore National Laboratories, Livermore, CA, USA.
Alice WongDepartment of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA, USA.
Benjamin OsipovDepartment of Orthopaedic Surgery, UC Davis Health, University of California, Sacramento, CA, USA.
Blaine A ChristiansenDepartment of Orthopaedic Surgery, UC Davis Health, University of California, Sacramento, CA, USA.
Gabriela G LootsLawrence Livermore National Laboratories, Livermore, CA, USA; Department of Orthopaedic Surgery, UC Davis Health, University of California, Sacramento, CA, USA.
Alexander G RoblingDepartment of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Clare E YellowleyDepartment of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA, USA.
Damian C GenetosDepartment of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA, USA. Electronic address: dgenetos@ucdavis.edu.

Funding

UC Davis MCB T32 Administrative Supplement to Recognize Excellence in Diversity, Equity, Inclusion, and Accessibility (DEIA) MentorshipT32GM007377 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI CHEDIN, FREDERIC LOUIS · 1985 to 2023
$9.9M
Osteocytic Vhl: Unlocking HIF-Independent Pathways in Bone AnabolismR01AR073772 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DAMIAN C GENETOS, Clare E Yellowley-Genetos · 2019 to 2026
$3.0M
NIAMS NIH HHS R01 AR073772NIGMS NIH HHS T32 GM007377
6 · The paper itself

Abstract

Skeletal fracture resistance emerges from multiple components of bone structure like microarchitecture, matrix mineralization, and organization. These characteristics are engendered via mechanisms like the hypoxia-inducible factors (HIF) pathway, involving two paralogs, HIF-1α and HIF-2α. Under normoxia, HIF-α is targeted for degradation via von-Hippel Lindau (VHL); hypoxia enables HIF-α stabilization and induction of target genes. We previously showed that osteocytic Vhl deletion or expression of degradation-resistant HIF-2α cDR female mice each produced high bone mass, whereas degradation-resistant osteocytic HIF-1α produced no overt phenotype. We report within that Vhl cKO increased bone strength, while HIF-2α cDR displayed markedly reduced bone strength below Cre-negative controls. This suggests that VHL and HIF-2α drive distinct responses that promote disparate effects on bone strength. Both Vhl deletion or HIF-2α accumulation generated two discrete bone morphologies: an outer lamellar cortex and a woven, poorly mineralized endocortex that imparted dramatically different functional outcomes. Our studies reveal novel influence of osteocytic HIF-2α signaling on collagen matrix organization, mineralization, and bone strength.

Indexed as

Basic Helix-Loop-Helix ProteinsBone and BonesOsteocytesOxygenVon Hippel-Lindau Tumor Suppressor ProteinAnimalsEndothelial PAS Domain-Containing Protein 1FemaleMiceBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1OxygenVHL protein, mouseVon Hippel-Lindau Tumor Suppressor ProteinCollagenHIFHigh bone massHypoxiaHypoxia inducible factorMineralizationOsteocyteVon Hippel Lindau

Identifiers

PMID39603372
PMCPMC12990954

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.