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Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling
- Source :
- Cell Death and Disease, Vol 9, Iss 10, Pp 1-18 (2018)
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- The prevascularization of tissue-engineered bone grafts (TEBGs) has been shown to accelerate capillary vessel ingrowth in bone defect remodeling and to enhance new bone formation. However, the exact mechanisms behind this positive effect remain unknown. Here, we report that basic fibroblast growth factor (FGF2)-Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) signaling functions as a molecular switch to regulate the lineage fate of bone mesenchymal stem cells (BMSCs) and that prevascularization promotes the cell fate switch, which contributes to increased bone regeneration with the use of prevascularized TEBGs compared with control TEBGs. Prevascularized TEBGs enhanced the in vivo endothelial differentiation of BMSCs by inhibiting RhoA/ROCK signaling. In vitro data more clearly showed that BMSCs differentiated into von Willebrand factor (vWF)-positive endothelial cells, and FGF2-induced inhibition of RhoA/ROCK signaling played a key role. Our novel findings uncovered a new mechanism that stimulates the increased vascularization of engineered bone and enhanced regeneration by promoting the endothelial differentiation of BMSCs implanted in TEBGs. These results offer a new molecular target to regulate TEBG-induced bone regeneration.
- Subjects :
- 0301 basic medicine
Cancer Research
Bone Regeneration
RHOA
Immunology
Basic fibroblast growth factor
Cell fate determination
Bone and Bones
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Tissue engineering
Animals
Humans
lcsh:QH573-671
Protein kinase A
Bone regeneration
rho-Associated Kinases
Tissue Engineering
biology
lcsh:Cytology
Regeneration (biology)
Mesenchymal stem cell
Endothelial Cells
Mesenchymal Stem Cells
Cell Biology
Rats
Cell biology
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
biology.protein
Female
Fibroblast Growth Factor 2
rhoA GTP-Binding Protein
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 9
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....57169f74c21711fea2a3dfdbbc201016