Role of YAP1 gene in proliferation, osteogenic differentiation, and apoptosis of human periodontal ligament stem cells induced by TNF‐α

Abstract

Background Periodontitis is a chronic inflammatory disease that occurs in periodontal tissues and can cause tooth loosening and loss in severe cases. As the main effector of downstream of Hippo signaling pathway, yes‐related protein 1 (YAP1) plays an important role in cell proliferation and differentiation. However, the role of YAP1 in periodontitis has not been reported. Methods Cell activity was detected by Cell Counting Kit‐8 (CCK‐8). YAP1 was overexpressed by cell transfection, and then RT‐qPCR and western blot were used to detect the expression of YAP1. The cell proliferation was determined by clone formation assay, and the expression of proliferation‐related proteins was determined by western blot. The cell differentiation was detected by ELISA kit of alkaline phosphatase activity (ALP) and alizarin red staining. Finally, western blot was used to detect the expression of differentiation‐related protein and Hippo signaling pathway‐related proteins. Apoptosis was detected by flow cytometry. Results With the increase of concentration induced by TNF‐α, the cell survival rate of human periodontal ligament stem cells (HPDLSCs) decreased significantly. After the overexpression of YAP1, cell proliferation and proliferation‐related protein expression increased. Overexpression of YAP1 can improve the differentiation and the formation of osteoblasts of HPDLSCs induced by TNF‐α. The expression of Hippo signaling pathway‐related proteins transcriptional coactivators with PDZ binding domains (TAZ), TEA domain family member (TRED) increased and proliferation‐related protein P27 decreased, whereas there was no significant change in the expression of MST1. Conclusion TNF‐α can inhibit proliferation and osteogenic differentiation of HPDLSCs, which can be ameliorated by the YAP1 gene through the Hippo signaling pathway. Our paper suggested that YAP1 may be a potential therapeutic target for periodontitis.

Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment

“…And other researchers also used 20 ng/mL or 50 ng/mL TNF- α to mimic the inflammatory microenvironment, which supported results. As the same, those also reckoned that proliferation rate was evidently suppressed and inflammatory cytokines expressed most on 72 hours [ 46 , 48 , 49 ].…”

Molecular Basis of the Curative Effects of Turkish Gall Extracts on Periodontitis

“…Our analysis revealed that TNF pathway–mediated apoptosis is involved in periodontitis progression (Figure 7). TNF‐α induces apoptosis in human periodontal ligament stem cells [34] . In vitro experiments further demonstrated that Turkish galls significantly reduced the level of inflammatory cytokines IL‐6 and TNF‐α.…”

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…Consequently, transcriptional YAP targets, such as cysteine-rich angiogenic inducer 61 (CYR61) and connective tissue growth factor (CTGF), are transcriptionally upregulated. By additionally inducing key differentiation markers of osteoblasts-amongst others, runt-related transcription factor 2 (RUNX2), osterix (OSX), osteopontin (OPN), and alkaline phosphatase-YAP is also involved in supporting the differentiation of PDLCs into osteoblasts (Figure 2) [141][142][143]. An orthodontic tooth movement (OTM) rat model as well as PDLCs in vitro experiments specifically proved that not only YAP but also TAZ supports osteogenic differentiation.…”