Glucose Restriction Promotes Osteocyte Specification by Activating a PGC-1α-Dependent Transcriptional Program
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| Titel: | Glucose Restriction Promotes Osteocyte Specification by Activating a PGC-1α-Dependent Transcriptional Program |
|---|---|
| Autoren: | Sánchez de Diego, Cristina, Artigas, Natalia, Pimenta-Lopes, Carolina, Valer, José Antonio, Torrejón-Escribano, Benjamín, Gama-Perez, Pau, Villena, Josep A., García-Roves, Pablo M. (Pablo Miguel), Rosa López, José Luis, Ventura Pujol, Francesc |
| Weitere Verfasser: | Institut Català de la Salut, [Sánchez-de-Diego C, Artigas N, Pimenta-Lopes C, Valer JA, Gama-Pérez P] Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, L'Hospitalet de Llobregat, Spain. [Torrejon B] Centres Científics i Tecnològics, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain. [Villena JA] Laboratori de Metabolisme i Obesitat, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain., Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona |
| Quelle: | iScience Scientia Scientia. Dipòsit d'Informació Digital del Departament de Salut instname Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Articles publicats en revistes (Ciències Fisiològiques) Dipòsit Digital de la UB Universidad de Barcelona iScience, Vol 15, Iss, Pp 79-94 (2019) |
| Verlagsinformationen: | Elsevier BV, 2019. |
| Publikationsjahr: | 2019 |
| Schlagwörter: | 0301 basic medicine, ANATOMY::Cells::Connective Tissue Cells::Osteoblasts::Osteocytes, Science, Cèl·lules, Cells, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Differentiation, ADN mitocondrial, Article, Molecular Physiology, CHEMICALS AND DRUGS::Carbohydrates::Sugars::Monosaccharides::Hexoses::Glucose, 03 medical and health sciences, Osteòcits - Fisiologia, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::diferenciación celular, COMPUESTOS QUÍMICOS Y DROGAS::hidratos de carbono::azúcares::monosacáridos::hexosas::glucosa, 0303 health sciences, ANATOMÍA::células::células del tejido conectivo::osteoblastos::osteocitos, Specialized Functions of Cells, Otros calificadores::Otros calificadores::Otros calificadores::Otros calificadores::/deficiencia, Mitochondrial DNA, Malalties dels ossos, Glucose, Other subheadings::Other subheadings::/physiology, Other subheadings::Other subheadings::Other subheadings::Other subheadings::/deficiency, Glucosa, Otros calificadores::Otros calificadores::/fisiología, Molecular Mechanism of Behavior, Diferenciació cel·lular, Bone diseases |
| Beschreibung: | 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. |
| Publikationsart: | Article Other literature type |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2019.04.015 |
| Zugangs-URL: | http://www.cell.com/article/S2589004219301129/pdf https://pubmed.ncbi.nlm.nih.gov/31039455 https://hdl.handle.net/11351/4163 https://hdl.handle.net/2445/162064 http://hdl.handle.net/2445/162064 https://doaj.org/article/ca5492442f6c4bf998c1bcc21a938f51 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488568 http://diposit.ub.edu/dspace/bitstream/2445/162064/1/690043.pdf https://europepmc.org/article/MED/31039455 http://diposit.ub.edu/dspace/handle/2445/162064 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488568 https://www.cell.com/article/S2589004219301129/pdf |
| Rights: | CC BY NC ND CC BY |
| Dokumentencode: | edsair.doi.dedup.....71b1c20de828f7a4ac6eeea40f91fe9d |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | 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. |
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| ISSN: | 25890042 |
| DOI: | 10.1016/j.isci.2019.04.015 |