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iScience. 2019 May 31;15:79-94. doi: 10.1016/j.isci.2019.04.015. Epub 2019 Apr 12.

Glucose Restriction Promotes Osteocyte Specification by Activating a PGC-1α-Dependent Transcriptional Program.

Author information

1
Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
2
Centres Científics i Tecnològics, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona 08907, Spain.
3
Laboratory of Metabolism and Obesity, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona 08035, Spain.
4
Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. Electronic address: fventura@ub.edu.

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.

KEYWORDS:

Molecular Mechanism of Behavior; Molecular Physiology; Specialized Functions of Cells

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