Hyperglycemic microenvironment compromises the homeostasis of communication between the bone-brain axis by the epigenetic repression of the osteocalcin receptor, Gpr158 in the hippocampus
dc.contributor.author | Patricia da Silva, Ericka | |
dc.contributor.author | da Silva Feltran, Geórgia [UNESP] | |
dc.contributor.author | Alexandre Alcântara dos Santos, Sérgio [UNESP] | |
dc.contributor.author | Cardoso de Oliveira, Rodrigo | |
dc.contributor.author | Assis, Rahyza I.F. | |
dc.contributor.author | Antônio Justulin Junior, Luis [UNESP] | |
dc.contributor.author | Carleto Andia, Denise | |
dc.contributor.author | Zambuzzi, Willian F. [UNESP] | |
dc.contributor.author | Latini, Alexandra | |
dc.contributor.author | Foganholi da Silva, Rodrigo A. | |
dc.contributor.institution | Paulista University – UNIP | |
dc.contributor.institution | University of Taubaté – UNITAU | |
dc.contributor.institution | Universidade Estadual Paulista (UNESP) | |
dc.contributor.institution | Universidade de São Paulo (USP) | |
dc.contributor.institution | Federal University of Espírito Santo | |
dc.contributor.institution | Universidade Federal de Santa Catarina (UFSC) | |
dc.date.accessioned | 2023-07-29T14:00:31Z | |
dc.date.available | 2023-07-29T14:00:31Z | |
dc.date.issued | 2023-03-15 | |
dc.description.abstract | Diabetes mellitus (DM) is a chronic metabolic disease, mainly characterized by increased blood glucose and insulin dysfunction. In response to the persistent systemic hyperglycemic state, numerous metabolic and physiological complications have already been well characterized. However, its relationship to bone fragility, cognitive deficits and increased risk of dementia still needs to be better understood. The impact of chronic hyperglycemia on bone physiology and architecture was assessed in a model of chronic hyperglycemia induced by a single intraperitoneal administration of streptozotocin (STZ; 55 mg/kg) in Wistar rats. In addition, the bone-to-brain communication was investigated by analyzing the gene expression and methylation status of genes that encode the main osteokines released by the bone [Fgf23 (fibroblast growth factor 23), Bglap (bone gamma-carboxyglutamate protein) and Lcn2 (lipocalin 2) and their receptors in both, the bone and the brain [Fgfr1 (fibroblast growth factor receptor 1), Gpr6A (G-protein coupled receptor family C group 6 member A), Gpr158 (G protein-coupled receptor 158) and Slc22a17 (Solute carrier family 22 member 17)]. It was observed that chronic hyperglycemia negatively impacted on bone biology and compromised the balance of the bone-brain endocrine axis. Ultrastructural disorganization was accompanied by global DNA hypomethylation and changes in gene expression of DNA-modifying enzymes that were accompanied by changes in the methylation status of the osteokine promoter region Bglap and Lcn2 (lipocalin 2) in the femur. Additionally, the chronic hyperglycemic state was accompanied by modulation of gene expression of the osteokines Fgf23 (fibroblast growth factor 23), Bglap (bone gamma-carboxyglutamate protein) and Lcn2 (lipocalin 2) in the different brain regions. However, transcriptional regulation mediated by DNA methylation was observed only for the osteokine receptors, Fgfr1(fibroblast growth factor receptor 1) in the striatum and Gpr158 (G protein-coupled receptor 158) in the hippocampus. This is a pioneer study demonstrating that the chronic hyperglycemic state compromises the crosstalk between bone tissue and the brain, mainly affecting the hippocampus, through transcriptional silencing of the Bglap receptor by hypermethylation of Gpr158 gene. | en |
dc.description.affiliation | CEEpiRG Program in Environmental and Experimental Pathology Paulista University – UNIP, São Paulo | |
dc.description.affiliation | Department of Dentistry University of Taubaté – UNITAU, São Paulo | |
dc.description.affiliation | Laboratory of Bioassays and Cellular Dynamics Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University – UNESP, São Paulo | |
dc.description.affiliation | School of Dentistry Health Science Institute Paulista University – UNIP, São Paulo | |
dc.description.affiliation | Department of Biological Sciences Bauru School of Dentistry University of São Paulo –FOB, São Paulo | |
dc.description.affiliation | Department of Clinical Dentistry Federal University of Espírito Santo, ES | |
dc.description.affiliation | LABOX Department of Biochemistry Center for Biological Sciences Federal University of Santa Catarina – UFSC | |
dc.description.affiliation | Department of Structural and Functional Biology Institute of Biosciences São Paulo State University – UNESP, São Paulo | |
dc.description.affiliationUnesp | Laboratory of Bioassays and Cellular Dynamics Department of Chemical and Biological Sciences Institute of Biosciences São Paulo State University – UNESP, São Paulo | |
dc.description.affiliationUnesp | Department of Structural and Functional Biology Institute of Biosciences São Paulo State University – UNESP, São Paulo | |
dc.identifier | http://dx.doi.org/10.1016/j.brainres.2023.148234 | |
dc.identifier.citation | Brain Research, v. 1803. | |
dc.identifier.doi | 10.1016/j.brainres.2023.148234 | |
dc.identifier.issn | 1872-6240 | |
dc.identifier.issn | 0006-8993 | |
dc.identifier.scopus | 2-s2.0-85146094181 | |
dc.identifier.uri | http://hdl.handle.net/11449/249029 | |
dc.language.iso | eng | |
dc.relation.ispartof | Brain Research | |
dc.source | Scopus | |
dc.subject | Bone-brain axis | |
dc.subject | Cognitive deficit | |
dc.subject | FGF23 | |
dc.subject | Lipocalin 2 | |
dc.subject | Osteocalcin | |
dc.title | Hyperglycemic microenvironment compromises the homeostasis of communication between the bone-brain axis by the epigenetic repression of the osteocalcin receptor, Gpr158 in the hippocampus | en |
dc.type | Artigo | |
unesp.department | Ciências Biológicas - FC | pt |