Shear stress-triggered adenosine triphosphate regulates angiogenic properties of human periodontal ligament stem cells

Abstract Mechanical forces stimulate human periodontal ligament stem cells (HPDLSCs) to release extracellular adenosine triphosphate (eATP). The eATP impacts various functions of HPDLSCs, i.e., immunosuppression and inflammation. eATP has been reported to promote the angiogenesis of pulmonary vascul...

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Main Authors: Maythwe Kyawsoewin, Jeeranan Manokawinchoke, Chutimon Termkwanchareon, Hnin Yu Lwin, Sanicha Yaklai, Nuttapol Limjeerajarus, Chalida Nakalekha Limjeerajarus, Hiroshi Egusa, Thanaphum Osathanon, Phoonsuk Limraksasin
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12323-w
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Summary:Abstract Mechanical forces stimulate human periodontal ligament stem cells (HPDLSCs) to release extracellular adenosine triphosphate (eATP). The eATP impacts various functions of HPDLSCs, i.e., immunosuppression and inflammation. eATP has been reported to promote the angiogenesis of pulmonary vascular endothelial cells. Shear force, one of the mechanical forces involved in orthodontic tooth movement, influences osteogenic differentiation and ECM remodeling of HPDLSCs. However, the relationship between shear force and the impact of eATP on endothelial differentiation and angiogenic characteristics of HPDLSCs remains unclear. This study aimed to determine the response of HPDLSCs on endothelial differentiation and angiogenic properties after shear stress loading and eATP treatment as well as explored the mechanism of eATP-involved in angiogenic responses of HPDLSCs. Shear stress application at 5 dyn/cm2 for 24 h stimulated the release of ATP by HPDLSCs. Both shear stress and 200 µM eATP promoted the expression of endothelial differentiation and angiogenic markers (ANG1, CD31, EPCR, e-selectin, FLK1, TIE2, VEGF). Blockade of specific P2Y1 receptor and intracellular calcium signaling attenuated eATP-induced expression of endothelial differentiation and angiogenic expression. Both shear stress and eATP have stimulatory effects on endothelial differentiation and angiogenesis in HPDLSCs through P2Y1-intracellular calcium signaling.
ISSN:2045-2322