Transcriptional factor ATF6 is involved in odontoblastic differentiation.

Kim, J W; Choi, H; Jeong, B C; Oh, S H; Hur, S W; Lee, B N; Kim, S H; Nör, J E; Koh, J T; Hwang, Y C

Kim, J W; Choi, H; Jeong, B C; Oh, S H; Hur, S W; Lee, B N; Kim, S H; Nör, J E; Koh, J T; Hwang, Y C.

Afiliación

Kim JW; Department of Conservative Dentistry, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea.

J Dent Res ; 93(5): 483-9, 2014 May.

Article en En | MEDLINE | ID: mdl-24570149

RESUMEN

ATF6 is an endoplasmic reticulum (ER) membrane-bound transcription factor that regulates various cellular functions. The purpose of this study was to investigate the role of ATF6 in odontoblast differentiation. Rat tooth germs were isolated, changes in gene expression were evaluated over time, and localization of ATF6 was determined by immunohistochemistry. Human dental pulp cells (HDPCs) were cultured with 50 µg/mL ascorbic acid and 5 mmol/L ß-glycerophosphate or 100 ng/mL bone morphogenetic protein 2 to induce differentiation. Translocation of ATF6 was observed by immunofluorescence and confocal microscopy. Overexpression of ATF6 was performed with an adenoviral vector. Matrix mineralization was evaluated by alizarin red staining. Immunoreactivity to anti-ATF6 was observed in the odontoblastic layer of the molar tooth germ, and expressions of ATF6, dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) increased gradually during tooth germ development. When HDPCs were cultured in differentiation media, ATF6, DSPP, and DMP1 expression increased with the expression of unfolded protein response (UPR) markers, BiP and CHOP. Immunofluorescence results showed that ATF6 protein moved from cytoplasm to nucleus when cells were exposed to differentiation media. Notably, overexpression of ATF6 increased DSPP and DMP1 expression, alkaline phosphatase (ALP) activity, and matrix mineralization in HDPC cultures. Inhibition of ATF6 decreased ALP activity and mineralization. These results suggest that ER membrane-bound transcriptional factor ATF6 may be involved in odontoblastic differentiation.

Asunto(s)

Factor de Transcripción Activador 6/fisiología; Odontoblastos/fisiología; Factor de Transcripción Activador 6/análisis; Adenoviridae/genética; Fosfatasa Alcalina/análisis; Animales; Proteína Morfogenética Ósea 2/farmacología; Calcificación Fisiológica/fisiología; Técnicas de Cultivo de Célula; Diferenciación Celular/efectos de los fármacos; Diferenciación Celular/fisiología; Línea Celular; Núcleo Celular/ultraestructura; Citoplasma/ultraestructura; Pulpa Dental/citología; Proteínas de la Matriz Extracelular/análisis; Regulación de la Expresión Génica/genética; Vectores Genéticos/genética; Humanos; Odontoblastos/efectos de los fármacos; Fosfoproteínas/análisis; Ratas; Ratas Sprague-Dawley; Sialoglicoproteínas/análisis; Germen Dentario/citología; Germen Dentario/crecimiento & desarrollo; Factor de Transcripción CHOP/análisis; Respuesta de Proteína Desplegada/fisiología

Palabras clave

DMP1; DSPP; ER stress; matrix mineralization; tooth development; unfolded protein response

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Transcripción Activador 6 / Odontoblastos Límite: Animals / Humans Idioma: En Revista: J Dent Res Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos

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