Evidence map›Paper›PMID 23998634›Full record

ArticleTissue engineering. Part C, Methods2014

Mild heat stress enhances angiogenesis in a co-culture system consisting of primary human osteoblasts and outgrowth endothelial cells.

Ming Li, Sabine Fuchs, Thomas Böse, Harald Schmidt, Alexander Hofmann, Marcus Tonak, Ronald Unger, Charles James Kirkpatrick

Abstract read
In one paragraph

Article in Tissue engineering. Part C, Methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

22 citing papers in PubMed, 49 citations in OpenAlex.

  1. Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle.American journal of physiology. Regulatory, integrative and comparative physiology · 2016
    Trial
  2. Article
  3. Article
  4. Effects of Thermal Environment on Bone Microenvironment: A Narrative Review.International journal of molecular sciences · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Effects of Twelve Sessions of High-Temperature Sauna Baths on Body Composition in Healthy Young Men.International journal of environmental research and public health · 2021
    Article
  13. Article
  14. Review
  15. Review
  16. Skeletal muscle adaptations to heat therapy.Journal of applied physiology (Bethesda, Md. : 1985) · 2020
    Article
  17. Vascular biology (Bristol, England) · 2019
    Review
  18. Article
  19. Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy.International journal of molecular sciences · 2018
    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

8 authors at 2 institutions in 2 countries.

Ming Li1 REPAIR-Lab, Institute of Pathology, University Medical Centre of the Johannes Gutenberg University , Mainz, Germany .
Sabine Fuchs
Thomas Böse
Harald Schmidt
Alexander Hofmann
Marcus Tonak
Ronald Unger
Charles James Kirkpatrick
Johannes Gutenberg University Mainz · DECollege of Metaphysical Studies · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The repair and regeneration of large bone defects, including the formation of functional vasculature, represents a highly challenging task for tissue engineering and regenerative medicine. Recent studies have shown that vascularization and ossification can be stimulated by mild heat stress (MHS), which would offer the option to enhance the bone regeneration process by relatively simple means. However, the mechanisms of MHS-enhanced angiogenesis and osteogenesis, as well as potential risks for the treated cells are unclear. We have investigated the direct effect of MHS on angiogenesis and osteogenesis in a co-culture system of human outgrowth endothelial cells (OECs) and primary osteoblasts (pOBs), and assessed cytotoxic effects, as well as the levels of various heat shock proteins (HSPs) synthesized under these conditions. Enhanced formation of microvessel-like structures was observed in co-cultures exposed to MHS (41°C, 1 h), twice per week, over a time period of 7-14 days. As shown by real-time polymerase chain reaction (PCR), the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and tumor necrosis factor-alpha was up-regulated in MHS-treated co-cultures 24 h post-treatment. At the protein level, significantly elevated VEGF and Ang-1 concentrations were observed in MHS-treated co-cultures and pOB mono-cultures compared with controls, indicating paracrine effects associated with MHS-induced angiogenesis. MHS-stimulated co-cultures and OEC mono-cultures released higher levels of Ang-2 than untreated cultures. On the other hand MHS treatment of co-cultures did not result in a clear effect regarding osteogenesis. Nevertheless, real-time PCR demonstrated that MHS increased the expression of mitogen-activated protein kinase, interleukin-6, and bone morphogenetic protein 2, known as HSP-related molecules in angiogenic and osteogenic regulation pathways. In agreement with these observations, the expression of some selected HSPs also increased at both the mRNA and protein levels in MHS-treated co-cultures.

Indexed as

Heat-Shock ResponseHot TemperatureNeovascularization, PhysiologicApoptosisCapillariesCaspase 3Caspase 7Cell DifferentiationCells, CulturedCell SurvivalCoculture TechniquesEndothelial CellsHumansOsteoblastsOsteogenesisRNA, MessengerCaspase 3Caspase 7RNA, Messenger

Identifiers

PMID23998634
PMCPMC3968880
OpenAlexW2036293352

What OpenQuestion holds

Textmetadata
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.