RICK regulates the odontogenic differentiation of dental pulp stem cells through activation of TNF‐α via the ERK and not through NF‐κB signaling pathway. (25th January 2021)

• Record Type: Journal Article
• Authors: Zhang, Ye; Lian, Min; Zhao, Xin; Cao, Peipei; Xiao, Jingwen; Shen, Shuling; Tang, Wanxian; Zhang, Jiaxuan; Hao, Jie; Feng, Xingmei
• Other Names: Sibirny Andrei guestEditor.
• Is Part Of: Cell biology international. Volume 45:Number 3(2021)
• Page Start: 569
• Page End: 579
• Publication Date: 2021-01-25
• Subjects: dental pulp stem cells (DPSCs) -- ERKs -- odontogenic differentiation -- RICK -- TNF‐α; Cytology -- Periodicals; Cells -- Periodicals; 571.605
• DOI: 10.1002/cbin.11498
• Languages: English
• ISSNs: 1065-6995

Abstract

Abstract: Dental pulp stem cells (DPSCs) are capable of both self‐renewal and multilineage differentiation, which play a positive role in dentinogenesis. Studies have shown that tumor necrosis factor‐α (TNF‐α) is involved in the differentiation of DPSCs under pro‐inflammatory stimuli, but the mechanism of action of TNF‐α is unknown. Rip‐like interacting caspase‐like apoptosis‐regulatory protein kinase (RICK) is a biomarker of an early inflammatory response that plays a key role in modulating cell differentiation, but the role of RICK in DPSCs is still unclear. In this study, we identified that RICK regulates TNF‐α‐mediated odontogenic differentiation of DPSCs via the ERK signaling pathway. The expression of the biomarkers of odontogenic differentiation dental matrix protein‐1 (DMP‐1), dentin sialophosphoprotein (DSPP), biomarkers of odontogenic differentiation, increased in low concentration (1–10 ng/ml) of TNF‐α and decreased in high concentration (50–100 ng/ml). Odontogenic differentiation increased over time in the odontogenic differentiation medium. In the presence of 10 ng/L TNF‐α, the expression of RICK increased gradually over time, along with odontogenic differentiation. Genetic silencing of RICK expression reduced the expression of odontogenic markers DMP‐1 and DSPP. The ERK, but not the NF‐κB signaling pathway, was activated during the odontogenic differentiation of DPSCs. ERK signaling modulators decreased when RICK expression was inhibited. PD98059, an ERK inhibitor, blocked the odontogenic differentiation of DPSCs induced by TNF‐α. These results provide a further theoretical and experimental basis for the potential use of RICK in targeted therapy for dentin regeneration.