RAC1 regulate tumor necrosis factor-α-mediated impaired osteogenic differentiation of dental pulp stem cells.
Dev Growth Differ
; 57(7): 497-506, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26219349
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/ß-catenin signaling pathway and liberate ß-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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Células-Tronco
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Diferenciação Celular
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Fator de Necrose Tumoral alfa
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Proteínas rac1 de Ligação ao GTP
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Polpa Dentária
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article