Evidence map›Paper›PMID 34465741›Full record

ArticleBone research2021

3D assessment of intervertebral disc degeneration in zebrafish identifies changes in bone density that prime disc disease.

Erika Kague, Francesco Turci, Elis Newman, Yushi Yang, Kate Robson Brown, Mona S Aglan, Ghada A Otaify, Samia A Temtamy, Victor L Ruiz-Perez, Stephen Cross and 3 more

Open access · goldAbstract read
In one paragraph

Article in Bone research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. DDRGK1 preserves intervertebral disc development through ufmylation.Cellular and molecular life sciences : CMLS · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. MicroCT Scanning and Analysis of the Zebrafish Skeleton.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Standardization of bone morphometry and mineral density assessments in zebrafish and other small laboratory fishes using X-ray radiography and micro-computed tomography.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Article
  17. Article
  18. Article
  19. Review
  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

13 authors at 4 institutions in 4 countries.

Erika KagueSchool of Physiology, Pharmacology and Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK. erika.kague@bristol.ac.uk.ORCID http://orcid.org/0000-0002-0266-9424
Francesco TurciSchool of Physics, HH Wills Physics Laboratory, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-0687-0715
Elis NewmanSchool of Physiology, Pharmacology and Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-3365-3943
Yushi YangSchool of Physics, HH Wills Physics Laboratory, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-6401-8088
Kate Robson BrownDepartment of Anthropology and Archaeology, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-4797-8965
Mona S AglanClinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.ORCID http://orcid.org/0000-0002-0908-0639
Ghada A OtaifyClinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.ORCID http://orcid.org/0000-0003-2313-7387
Samia A TemtamyClinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.ORCID http://orcid.org/0000-0002-6452-823X
Victor L Ruiz-PerezInstituto de Investigaciones, Biomedicas de Madrid, and Ciber de Enfermedades Raras (CIBERER), Madrid, Spain.ORCID http://orcid.org/0000-0003-0635-3619
Stephen CrossWolfson Bioimaging Facility, Biomedical Sciences, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-3565-0479
C Patrick RoyallSchool of Physics, HH Wills Physics Laboratory, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0001-7247-8685
P Eckhard WittenEvolutionary Developmental Biology, Department of Biology, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0002-2928-5762
Chrissy L HammondSchool of Physiology, Pharmacology and Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK. chrissy.hammond@bristol.ac.uk.ORCID http://orcid.org/0000-0002-4935-6724
University of Bristol · GBNational Research Centre · EGCentre for Biomedical Network Research on Rare Diseases · ESGhent University · BE

Funding

EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)) 617266 "NANOPRS"
6 · The paper itself

Abstract

Back pain is a common condition with a high social impact and represents a global health burden. Intervertebral disc disease (IVDD) is one of the major causes of back pain; no therapeutics are currently available to reverse this disease. The impact of bone mineral density (BMD) on IVDD has been controversial, with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for IVDD. Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing. By taking a holistic 3D approach, we established an aging zebrafish model for spontaneous IVDD. Increased BMD in aging, detected by automated computational analysis, is caused by bone deformities at the endplates. However, aged zebrafish spines showed changes in bone morphology, microstructure, mineral heterogeneity, and increased fragility that resembled osteoporosis. Elements of the discs recapitulated IVDD symptoms found in humans: the intervertebral ligament (equivalent to the annulus fibrosus) showed disorganized collagen fibers and herniation, while the disc center (nucleus pulposus equivalent) showed dehydration and cellular abnormalities. We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K, leading to low and high BMD, respectively. Remarkably, we detected IVDD in both groups, demonstrating that low BMD does not protect against IVDD, and we found a strong correlation between high BMD and IVDD. Deep learning was applied to high-resolution synchrotron µCT image data to analyze osteocyte 3D lacunar distribution and morphology, revealing a role of sp7 in controlling the osteocyte lacunar 3D profile. Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD.

Identifiers

PMID34465741
PMCPMC8408153
OpenAlexW3155446363

What OpenQuestion holds

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Registered trials

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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.