Evidence mapPaperPMID 38834586Full record

ArticleNature communications2024

Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration.

M Gabriele Bixel, Kishor K Sivaraj, Melanie Timmen, Vishal Mohanakrishnan, Anusha Aravamudhan, Susanne Adams, Bong-Ihn Koh, Hyun-Woo Jeong, Kai Kruse, Richard Stange and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing 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

46 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. 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

11 authors.

M Gabriele BixelDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany. mgbixel@mpi-muenster.mpg.de.ORCID http://orcid.org/0000-0001-8656-8075
Kishor K SivarajDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0002-5321-3400
Melanie TimmenDepartment of Regenerative Musculoskeletal Medicine, Institute of Musculoskeletal Medicine, University Hospital Münster, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0002-8487-9715
Vishal MohanakrishnanDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0003-0976-9230
Anusha AravamudhanDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0001-5934-6100
Susanne AdamsDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.
Bong-Ihn KohDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0002-3636-0492
Hyun-Woo JeongDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0002-6976-6739
Kai KruseDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0002-7951-7357
Richard StangeDepartment of Regenerative Musculoskeletal Medicine, Institute of Musculoskeletal Medicine, University Hospital Münster, D-48149, Münster, Germany.ORCID http://orcid.org/0000-0003-0807-3151
Ralf H AdamsDepartment of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of Münster, Faculty of Medicine, D-48149, Münster, Germany. ralf.adams@mpi-muenster.mpg.de.ORCID http://orcid.org/0000-0003-3031-7677

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)) AdG 786672 PROVEC
6 · The paper itself

Abstract

Bone regeneration requires a well-orchestrated cellular and molecular response including robust vascularization and recruitment of mesenchymal and osteogenic cells. In femoral fractures, angiogenesis and osteogenesis are closely coupled during the complex healing process. Here, we show with advanced longitudinal intravital multiphoton microscopy that early vascular sprouting is not directly coupled to osteoprogenitor invasion during calvarial bone regeneration. Early osteoprogenitors emerging from the periosteum give rise to bone-forming osteoblasts at the injured calvarial bone edge. Microvessels growing inside the lesions are not associated with osteoprogenitors. Subsequently, osteogenic cells collectively invade the vascularized and perfused lesion as a multicellular layer, thereby advancing regenerative ossification. Vascular sprouting and remodeling result in dynamic blood flow alterations to accommodate the growing bone. Single cell profiling of injured calvarial bones demonstrates mesenchymal stromal cell heterogeneity comparable to femoral fractures with increase in cell types promoting bone regeneration. Expression of angiogenesis and hypoxia-related genes are slightly elevated reflecting ossification of a vascularized lesion site. Endothelial Notch and VEGF signaling alter vascular growth in calvarial bone repair without affecting the ossification progress. Our findings may have clinical implications for bone regeneration and bioengineering approaches.

Indexed as

Bone RegenerationMesenchymal Stem CellsNeovascularization, PhysiologicOsteogenesisSkullAngiogenesisAnimalsFemaleMaleMiceMice, Inbred C57BLOsteoblastsReceptors, NotchSignal TransductionVascular Endothelial Growth Factor AReceptors, NotchVascular Endothelial Growth Factor A

Identifiers

PMID38834586
PMCPMC11150404

What Socratic 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 Socratic graph.