Sanchez-de-Diego 2019 iScience
|Sánchez-de-Diego C, Artigas N, Pimenta-Lopes C, Valer JA, Torrejon B, Gama-Pérez P, Villena JA, Garcia-Roves PM, Rosa JL, Ventura F (2019) Glucose restriction promotes osteocyte specification by activating a PGC-1α-dependent transcriptional program. iScience 15:79-94.|
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.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved. • Keywords: Molecular mechanism of behavior, Molecular physiology, Specialized functions of cells • Bioblast editor: Plangger M • O2k-Network Lab: ES Barcelona Garcia-Roves PM
Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression, Developmental biology
Organism: Mouse Tissue;cell: Other cell lines Preparation: Intact cells
Regulation: Substrate Coupling state: LEAK, ROUTINE, ET Pathway: ROX HRR: Oxygraph-2k