Topographic cues of a novel bilayered scaffold modulate dental pulp stem cells differentiation by regulating YAP signalling through cytoskeleton adjustments

Abstract

Objectives Topographic cues can modulate morphology and differentiation of mesenchymal stem cells. This study aimed to determine how topographic cues of a novel bilayered poly (lactic‐co‐glycolic acid) (PLGA) scaffold affect osteogenic/odontogenic differentiation of dental pulp stem cells (DPSCs). Methods The surface morphology of the scaffolds was visualized by scanning electron microscope, and the surface roughness was measured by profilometry. DPSCs were cultured on each side of the scaffolds. Cell morphology, expression of Yes‐associated protein (YAP) and osteogenic/odontogenic differentiation were analysed by immunohistochemistry, real‐time polymerase chain reaction, and Alizarin Red S staining. In addition, cytochalasin D (CytoD), an F‐actin disruptor, was used to examine the effects of F‐actin on intracellular YAP localisation. Verteporfin, a YAP transcriptional inhibitor, was used to explore the effects of YAP signalling on osteogenic/odontogenic differentiation of DPSCs. Results The closed side of our scaffold showed smaller pores and less roughness than the open side. On the closed side, DPSCs exhibited enhanced F‐actin stress fibre alignment, larger spreading area, more elongated appearance, predominant nuclear YAP localization and spontaneous osteogenic differentiation. Inhibition of F‐actin alignments was correlated with nuclear YAP exclusion of DPSCs. Verteporfin restricted YAP localisation to the cytoplasm, down‐regulated expression of early osteogenic/odontogenic markers and inhibited mineralization of DPSCs cultures. Conclusions The surface topographic cues changed F‐actin alignment and morphology of DPSCs, which in turn regulated YAP signalling to control osteogenic/odontogenic differentiation.

A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: Enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway

“…Yes-associated protein (YAP) is a key co-transcription factor in the Hippo signaling that plays an important role in vascular remodeling and can regulate VSMCs phenotype transition [ 18 ]. Generally, YAP induces VSMCs synthetic phenotype and promotes neointima formation through inhibiting smooth muscle-specific gene expression while promoting smooth muscle proliferation and migration in vitro and in vivo [ 19 , 20 ]. So, blocking the induction of YAP would be a potential therapeutic approach for ameliorating vascular occlusive diseases.…”

Mechanical Sensing Element PDLIM5 Promotes Osteogenesis of Human Fibroblasts by Affecting the Activity of Microfilaments

“…We also showed that knockdown of PDLIM5 significantly reduced the expression of YAP in the nucleus and its nuclear localization. The YAP pathway has been shown to be involved in the process of cell osteogenesis [50,51]. YAP signaling is one of the more studied and complex pathways involved in osteogenic differentiation.…”

Knowledge, attitude, and practice toward regenerative endodontics and factors affecting its practice among dental practitioners in Ajmer city: A cross-sectional study

“…In the present study, knowledge, attitude, and practice of dental practitioners and factors affecting their opinion toward regenerative endodontics were explored. The past many studies[915161718] have conducted to determine opinion of dental practitioners toward regenerative endodontics, but none of the studies has not assessed the factors affecting their judgment.…”

“…The recent technique developed in regenerative endodontics is controlling of odontogenic differentiation through involvement of Yes-associated protein. [17]…”