Work

Dentin sialoprotein promotes endothelial differentiation of dental pulp stem cells through DSPaa34–50–endoglin–AKT1 axis

Year: 2025

Type: article

Abstract: Dentin sialoprotein (DSP), a major dentin extracellular matrix non-collagenous protein, is well recognized as an important regulator for dentinogenesis. DSP as a secreted protein can interact with membrane receptors, activate intracellular signaling, and initiate the odontoblastic differentiation of dental papilla cells. In recent study, we have demonstrated that DSP can induce the endothelial differentiation of dental pulp stem cells (DPSCs), a type of tooth pulp-derived multipotent stem cells, dependent on membrane receptor endoglin (ENG). However, the intimate mechanisms by which DSP-ENG association facilitates the endothelial differentiation of DPSCs remain enigmatic. Here, we find that the amino acid (aa) residues 34-50 of DSP (DSP aa34-50 ) is responsible for its association with ENG using a series of co-immunoprecipitation assays. Immunofluorescent staining and in situ proximity ligation (PLA) assays demonstrate that overexpressed ENG in HEK293T cells show co-distribution and PLA signals to the supplemented DSP aa34-50 protein but not to DSP without aa34-50 (DSP Δ34-50 ) on cell surfaces. Moreover, the zona pellucida domain of ENG mediates its association with DSP aa34-50 . Further experiments indicate that DSP aa34-50 exhibits equivalent effects to the full-length DSP on the migration and endothelial differentiation of DPSCs dependent on ENG, but DSP Δ34-50 does not. Mechanistically, DSP aa34-50 activates AKT1 and triggers the expression of blood vessel development-related genes in DPSCs. Multiple experiments demonstrate that AKT1 inhibition suppresses the DSP aa34-50 -induced migration and endothelial differentiation of DPSCs. Thus, AKT1 mediates the cellular and molecular functions of DSP aa34-50 -ENG association. Collectively, these findings identify that DSP promotes the endothelial differentiation of DPSCs through the DSP aa34-50 -ENG-AKT1 signaling axis.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.108380

Authors: Ximin Xu, Jing Fu, Guobin Yang, Zhi Chen, Shuo Chen, Guohua Yuan

Institutions: Wuhan University, The University of Texas at San Antonio Health Science Center

Language: English

Topic: Bone and Dental Protein Studies

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430