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Peer-reviewedCC BY-NC-NDJournal of dental sciences

Exosomes derived from bone substitute-induced gingival mesenchymal stem cells promote angiogenesis.

  1. 1Yunnan Key Laboratory of Stomatology & Department of Oral Implantology, The Affiliated Stomatology Hospital, Kunming Medical University, Kunming, China.
  2. 2Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University (the First Hospital of Kunming), Kunming, China.
  3. 3Dehong Vocational College, Dehong, China.

Abstract

Background/purpose

In certain clinical bone grafting scenarios, bone substitutes frequently interface with the adjacent soft tissues. This study aimed to investigate whether deproteinized bovine bone mineral (DBBM) and coralline hydroxyapatite (CHA) induce paracrine responses in human gingival mesenchymal stem cells (GMSCs), thereby altering the pro-angiogenic capacity of their derived exosomes, and to profile specific cargo alterations.Materials and methods

Exosomes were isolated from GMSCs co-cultured with DBBM (DBBM-GEXO) or CHA (CHA-G-EXO), while native GMSCs-derived exosomes (G-EXO) were collected as controls. The angiogenic effects of these exosomes on human umbilical vein endothelial cells (HUVEC) were evaluated via cell proliferation, scratch wound healing, Western blot analysis, and Matrigel tube formation assays. Alterations in exosomal cargoes were profiled using data-independent acquisition (DIA) proteomics. The core identified exosomal protein was subsequently validated through specific antibody blockade.Results

Both bone substitutes supported robust GMSC attachment. Compared with native exosomes, DBBM-G-EXO and CHA-G-EXO significantly enhanced HUVEC proliferation, migration, and capillary-like network formation, while upregulating angiogenic markers. Proteomic analysis identified 206 commonly upregulated proteins in bone substitute-induced exosomes, showing significant enrichment in the "Angiogenesis" Gene Ontology (GO) term. Integrin beta-1 (ITGB1) occupied the central position in the protein network, aligning with its transcriptional upregulation in the induced GMSCs. Specific blockade of exosomal ITGB1 effectively abrogated the enhanced pro-angiogenic effects initially induced by the bone substitutes.Conclusion

DBBM and CHA induce the paracrine reprogramming of GMSCs, significantly enhancing the effects of GMSCs-derived exosomes in promoting angiogenesis via ITGB1 enrichment.

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BibTeX
@article{shen2026exosomes,
  title = {{Exosomes derived from bone substitute-induced gingival mesenchymal stem cells promote angiogenesis.}},
  author = {Chongyu Shen and Zheng Guan and Rui Chu and Zhengyin Li and Jiangting Lu and Liangkun Xie},
  journal = {Journal of dental sciences},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jds.2025.07.3695},
  url = {https://europepmc.org/article/MED/42923663},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Exosomes derived from bone substitute-induced gingival mesenchymal stem cells promote angiogenesis.
AU  - Chongyu Shen
AU  - Zheng Guan
AU  - Rui Chu
AU  - Zhengyin Li
AU  - Jiangting Lu
AU  - Liangkun Xie
PY  - 2026
DA  - 2026/10/01
JO  - Journal of dental sciences
DO  - 10.1016/j.jds.2025.07.3695
UR  - https://europepmc.org/article/MED/42923663
AB  - Background/purpose  In certain clinical bone grafting scenarios, bone substitutes frequently interface with the adjacent soft tissues. This study aimed to investigate whether deproteinized bovine bone mineral (DBBM) and coralline hydroxyapatite (CHA) induce paracrine responses in human gingival mesenchymal stem cells (GMSCs), thereby altering the pro-angiogenic capacity of their derived exosomes, and to profile specific cargo alterations.Materials and methods  Exosomes were isolated from GMSCs co-cultured with DBBM (DBBM-GEXO) or CHA (CHA-G-EXO), while native GMSCs-derived exosomes (G-EXO) were collected as controls. The angiogenic effects of these exosomes on human umbilical vein endothelial cells (HUVEC) were evaluated via cell proliferation, scratch wound healing, Western blot analysis, and Matrigel tube formation assays. Alterations in exosomal cargoes were profiled using data-independent acquisition (DIA) proteomics. The core identified exosomal protein was subsequently validated through specific antibody blockade.Results  Both bone substitutes supported robust GMSC attachment. Compared with native exosomes, DBBM-G-EXO and CHA-G-EXO significantly enhanced HUVEC proliferation, migration, and capillary-like network formation, while upregulating angiogenic markers. Proteomic analysis identified 206 commonly upregulated proteins in bone substitute-induced exosomes, showing significant enrichment in the "Angiogenesis" Gene Ontology (GO) term. Integrin beta-1 (ITGB1) occupied the central position in the protein network, aligning with its transcriptional upregulation in the induced GMSCs. Specific blockade of exosomal ITGB1 effectively abrogated the enhanced pro-angiogenic effects initially induced by the bone substitutes.Conclusion  DBBM and CHA induce the paracrine reprogramming of GMSCs, significantly enhancing the effects of GMSCs-derived exosomes in promoting angiogenesis via ITGB1 enrichment.
SN  - 1991-7902
SN  - 2213-8862
ER  -