title: RAC1 regulate tumor necrosis factor-α-mediated impaired osteogenic differentiation of dental pulp stem cells.
abstract: 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-α (TNF-α) (10 ng/mL) triggered osteogenic differentiation of human DPSCs via the nuclear factor-κB (NF-κB) signaling pathway. While previous studies showed that cells treated with TNF-α at higher concentrations showed decreased osteogenic differentiation capability. In this study we analyze the function of TNF-α (100 ng/mL) on osteogenic differentiation of human DPSCs for the first time and identify the underlying molecule mechanisms. Our data revealed that TNF-α 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-α could suppress the osteogenic differentiation of DPSCs via increasing the expression of RAC1, which could activate the Wnt/β-catenin signaling pathway and liberate β-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.
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Qijie
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lian
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology and Hepatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Liren
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Huang
authors.affiliation: Wang Yi Dental Clinic, Suzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Jiahai
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000473:pathology; D006801:Humans; D010012:Osteogenesis; D013234:Stem Cells / Q000166:cytology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C107953:RAC1 protein, human; D014409:Tumor Necrosis Factor-alpha; D020830:rac1 GTP-Binding Protein
keywords: RAC1; Wnt/β-catenin; dental pulp stem cells; osteogenic differentiation; tumor necrosis factor α