RAC1 regulate tumor necrosis factor--mediated impaired osteogenic differentiation of dental pulp stem cells

摘要

Human dental pulp contains a rapidly proliferative subpopulation of precursor cells termed dental pulp stem cells (DPSCs) that show self-renewal and multilineage differentiation, including neurogenic, chondrogenic, osteogenic and adipogenic. We previously reported that tomuor necrosis factor- (TNF-) (10ng/mL) triggered osteogenic differentiation of human DPSCs via the nuclear factor-B (NF-B) signaling pathway. While previous studies showed that cells treated with TNF- at higher concentrations showed decreased osteogenic differentiation capability. In this study we analyze the function of TNF- (100ng/mL) on osteogenic differentiation of human DPSCs for the first time and identify the underlying molecule mechanisms. Our data revealed that TNF- with higher concentration significantly reduced mineralization and the expression of bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX2). Further, we revealed that TNF- could suppress the osteogenic differentiation of DPSCs via increasing the expression of RAC1, which could activate the Wnt/-catenin signaling pathway and liberate -catenin to translocate into the nucleus. Genetic silencing of RAC1 expression using siRNA restored osteogenic differentiation of DPSCs. Our findings may provide a potential approach to bone regeneration in inflammatory microenvironments.