Glucose Restriction Promotes Osteocyte Specification by Activating a PGC-1α-Dependent Transcriptional Program
Sánchez-de-Diego, Cristina (Universitat de Barcelona)
Artigas, Natalia (Universitat de Barcelona)
Pimenta-Lopes, Carolina (Universitat de Barcelona)
Valer, José Antonio (Universitat de Barcelona)
Torrejon, Benjamin (Universitat de Barcelona)
Gama-Pérez, Pau (Universitat de Barcelona)
Villena, Josep A. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Roves, Pablo M. (Universitat de Barcelona)
Rosa, José Luis (Universitat de Barcelona)
Ventura, Francesc (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Date:	2019
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 while also being associated with increased mitochondrial DNA levels. 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. Molecular Mechanism of Behavior; Molecular Physiology; Specialized Functions of Cells.
Grants:	Ministerio de Economía y Competitividad BFU2014-56313-P
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Molecular Mechanism of Behavior ; Molecular Physiology ; Specialized Functions of Cells
Published in:	iScience, Vol. 15 (may 2019) , p. 79-94, ISSN 2589-0042

DOI: 10.1016/j.isci.2019.04.015
PMID: 31039455

42 p, 9.1 MB

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