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Published on: September 14, 2021
DPSCs-generated contraction force regulates vessel network morphogenesis via YAP1/TGF-β1/Smad2 signaling.
Yihan Chen1, Wen Wang1, Mingxin Hu1
1Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong Special Administrative Region of China.
Dental pulp stem cells (DPSCs) use contraction force, regulated by YAP1, to form new blood vessels. YAP1 is crucial for DPSC differentiation into smooth muscle cells, impacting vessel network development.
Area of Science:
- Regenerative Medicine
- Vascular Biology
- Stem Cell Biology
Background:
- Dental pulp stem cells (DPSCs) possess regenerative potential.
- Vessel formation (angiogenesis) is a complex process involving cellular forces and differentiation.
- The role of yes-associated protein 1 (YAP1) in DPSC-mediated vascularization is not fully understood.
Purpose of the Study:
- To investigate the contribution of DPSC-generated contraction force to vessel formation.
- To elucidate the role of YAP1 in DPSCs during this process.
Main Methods:
- DPSC contraction force was measured in fluorescently labeled gels.
- DPSCs were treated with TGF-β1, Cytochalasin D, and Y27632 to assess F-actin contractility and YAP1.
- YAP1's role in DPSC differentiation into smooth muscle cells (SMCs) and its impact on vascular morphology were evaluated.
Main Results:
- DPSCs enhanced matrix remodeling and controlled vascular network formation via contraction force.
- Reduced contractility in DPSCs treated with Y27632 and CytoD led to decreased YAP1 nuclear translocation.
- YAP1 knockdown in DPSCs reduced phosphorylated Smad2, decreased SMC marker expression, and impaired vessel network formation.
- In vivo studies showed increased vessel diameter and reduced endothelial cell survival in YAP1-deficient DPSC groups.
Conclusions:
- YAP1 in DPSCs regulates the TGF-β1/Smad2 pathway, promoting differentiation into SMCs.
- YAP1 enhances DPSC contractile force, which is essential for controlling vascular network formation and maintenance.
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