Evidence map›Paper›PMID 41540952›Full record

ArticleCell biochemistry and function2026

Venous Endothelial Cells Promote Osteoblast Differentiation More Effectively Than Arterial Cells via TGF-β/BMP9 and Notch Pathway-Related Gene Expression.

Célio J C Fernandes, Rodrigo A Foganholi da Silva, Marcel R Ferreira, Willian F Zambuzzi

Abstract read
In one paragraph

Article in Cell biochemistry and function, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

4 authors.

Célio J C FernandesBioassays and Cell Dynamics Lab, Department of Chemistry and Biochemistry, Bioscience Institute, UNESP: Universidade Estadual Paulista, Botucatu, Sao Paulo, Brazil.
Rodrigo A Foganholi da SilvaSchool of Dentistry, University of Taubaté, Taubaté, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-7754-1855
Marcel R FerreiraMolecular Genetics and Bioinformatics Laboratory, Experimental Research Unit - Unipex, School of Medicine, São Paulo State University - Unesp, Botucatu, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-3445-0945
Willian F ZambuzziBioassays and Cell Dynamics Lab, Department of Chemistry and Biochemistry, Bioscience Institute, UNESP: Universidade Estadual Paulista, Botucatu, Sao Paulo, Brazil.ORCID https://orcid.org/0000-0002-4149-5965

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo 2014/22689-3Fundação de Amparo à Pesquisa do Estado de São Paulo 2016/08888-9Fundação de Amparo à Pesquisa do Estado de São Paulo 2018/10856-3Fundação de Amparo à Pesquisa do Estado de São Paulo 2019/21807-6National Council for Scientific and Technological Development - CNPq 301498/2022-9National Council for Scientific and Technological Development - CNPq 408594/2024-1National Council for Scientific and Technological Development - CNPq WFZ: 312391/2025-0
6 · The paper itself

Abstract

The coupling between angiogenesis and osteogenesis is a key determinant of skeletal homeostasis, yet the influence of endothelial cell origin on osteoblast differentiation remains underexplored. Here, we investigated how venous (HUVECs) and arterial (HCAECs) endothelial cells differentially modulate the osteogenic phenotype of human osteoblasts via paracrine signaling. To better address this issue, the conditioned media (CM) from HUVECs significantly enhanced osteoblast differentiation, as evidenced by increased alkaline phosphatase activity, upregulation of canonical markers such as Runx2, Osterix, and Osteocalcin, and activation of matrix mineralization genes (Tnap, Bsp, Col1a1). In contrast, CM from HCAECs induced a markedly weaker response. qPCR analysis revealed that HUVEC-CM robustly stimulated key osteoinductive pathways, including TGF-β/BMP9 and Notch, with pronounced activation of SMADs, Jagged, and Notch receptors. Moreover, HUVEC-CM promoted cytoskeletal remodeling via increased expression of Integrin-β1, FAK, Src, and Cofilin, and favored ECM organization by repressing MMP activity and enhancing Reck expression. Hypoxia-associated markers (Hif1α, Vegf) were also elevated in HUVEC-treated osteoblasts, supporting enhanced angiogenic-osteogenic coupling. Principal component and network analyses confirmed a distinct molecular clustering for HUVEC-responsive genes. Altogether, our data demonstrate that venous endothelial cells, through their specific secretome, provide a more adequate microenvironment for osteoblast differentiation and mineralization compared to their arterial equivalent. These findings underscore the functional relevance of endothelial plasticity in bone regeneration and support the use of venous-derived endothelial factors in bone tissue engineering strategies.

Indexed as

ArteriesCell DifferentiationEndothelial CellsGrowth Differentiation Factor 2Human Umbilical Vein Endothelial CellsOsteoblastsReceptors, NotchSignal TransductionTransforming Growth Factor betaCells, CulturedCulture Media, ConditionedHumansOsteogenesisCulture Media, ConditionedGDF2 protein, humanGrowth Differentiation Factor 2Receptors, NotchTransforming Growth Factor betabone regenerationendothelial cellsHUVECosteogenesissignal transduction

Identifiers

PMID41540952
PMCPMC12809378

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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.