Reference

Sánchez-de-Diego, C., Artigas, N., Pimenta-Lopes, C., Valer, J. A., Torrejon, B., Gama-Pérez, P., Jose Antonio Villena, Pablo García Roves, Jose Luis Rosa & Ventura, F. (2019). Glucose restriction promotes osteocyte specification by activating a PGC-1α-dependent transcriptional program. iScience. https://doi.org/10.1016/j.isci.2019.04.015iscience

Authors

Cristina Sánchez de Diego, Natalia Artigas, Carolina Pimenta-Lopes, José Antonio Valer, Benjamin Torrejón, Pau Gama-Pérez, Jose Antonio Villena, Pablo García Roves, José Luis Rosa, Francesc Ventura.

Abstract

Osteocytes, the most abundant of bone cells, differentiate while they remain buried within the bone matrix. This encasement limits their access to nutrients and likely affects their differentiation, a process that remains poorly defined. Here, we show that restriction in glucose supply promotes the osteocyte transcriptional program associated with an increased mitochondrial function. Glucose deprivation triggered the activation of the AMPK/PGC-1 pathway. AMPK and SIRT1 activators or PGC-1α overexpression are sufficient to enhance osteocyte gene expression in IDG-SW3 cells, murine primary osteoblasts, osteocytes, and organotypic/ex vivo bone cultures. Conversely, osteoblasts and osteocytes deficient in Ppargc1a and b were refractory to the effects of glucose restriction. Finally, conditional ablation of both genes in osteoblasts and osteocytes generate osteopenia and reduce osteocytic gene expression in mice. Altogether, we uncovered a role for PGC-1 in the regulation of osteocyte gene expression.

Description

Los osteocitos son el principal componente celular del hueso. Además de sus importancia como mecanosensores, en los últimos años se le ha atribuido papeles clave en la regulación endocrina del metabolismo, así como en los procesos de remodelado óseo y hematopoyesis. Los osteocitos se forman a partir osteoblastos que continúan su proceso de diferenciación mientras quedan encerrados en la matriz ósea. En este trabajo hemos demostrado como la reducción en el aporte de glucosa y la activación de PGC-1α son etapas imprescindibles en el proceso de diferenciación osteocítica.

 

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REFERENCIA DEL GRUPO INVESTIGADOR

Nuestro grupo de investigación en la Universidad de Barcelona está dirigido por el Dr. Francesc Ventura. El grupo lleva años estudiando como alteraciones en vías señalización pueden modificar el metabolismo, la homeostasis y la regeneración ósea. El objetivo último es la obtención de nuevos métodos de tratamiento de patologías óseas por modificación de estas rutas metabólicas y de señalización celular.

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