Cargando…

Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells

It is important to understand whether endothelial cells are epigenetically affected by titanium-enriched media when angiogenesis is required during bone development and it is expected to be recapitulated during osseointegration of biomaterials. To better address this issue, titanium-enriched medium...

Descripción completa

Detalles Bibliográficos
Autores principales: Fernandes, Célio Júnior da C., da Silva, Rodrigo A. Foganholi, Wood, Patrícia F., Ferreira, Marcel Rodrigues, de Almeida, Gerson S., de Moraes, Julia Ferreira, Bezerra, Fábio J., Zambuzzi, Willian F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055987/
https://www.ncbi.nlm.nih.gov/pubmed/36976055
http://dx.doi.org/10.3390/jfb14030131
_version_ 1785016014438662144
author Fernandes, Célio Júnior da C.
da Silva, Rodrigo A. Foganholi
Wood, Patrícia F.
Ferreira, Marcel Rodrigues
de Almeida, Gerson S.
de Moraes, Julia Ferreira
Bezerra, Fábio J.
Zambuzzi, Willian F.
author_facet Fernandes, Célio Júnior da C.
da Silva, Rodrigo A. Foganholi
Wood, Patrícia F.
Ferreira, Marcel Rodrigues
de Almeida, Gerson S.
de Moraes, Julia Ferreira
Bezerra, Fábio J.
Zambuzzi, Willian F.
author_sort Fernandes, Célio Júnior da C.
collection PubMed
description It is important to understand whether endothelial cells are epigenetically affected by titanium-enriched media when angiogenesis is required during bone development and it is expected to be recapitulated during osseointegration of biomaterials. To better address this issue, titanium-enriched medium was obtained from incubation of titanium discs for up to 24 h as recommended by ISO 10993-5:2016, and further used to expose human umbilical vein endothelial cells (HUVECs) for up to 72 h, when the samples were properly harvested to allow molecular analysis and epigenetics. In general, our data show an important repertoire of epigenetic players in endothelial cells responding to titanium, reinforcing protein related to the metabolism of acetyl and methyl groups, as follows: Histone deacetylases (HDACs) and NAD-dependent deacetylase sirtuin-1 (Sirt1), DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) methylcytosine dioxygenases, which in conjunction culminate in driving chromatin condensation and the methylation profile of DNA strands, respectively. Taking our data into consideration, HDAC6 emerges as important player of this environment-induced epigenetic mechanism in endothelial cells, while Sirt1 is required in response to stimulation of reactive oxygen species (ROS) production, as its modulation is relevant to vasculature surrounding implanted devices. Collectively, all these findings support the hypothesis that titanium keeps the surrounding microenvironment dynamically active and so affects the performance of endothelial cells by modulating epigenetics. Specifically, this study shows the relevance of HDAC6 as a player in this process, possibly correlated with the cytoskeleton rearrangement of those cells. Furthermore, as those enzymes are druggable, it opens new perspectives to consider the use of small molecules to modulate their activities as a biotechnological tool in order to improve angiogenesis and accelerate bone growth with benefits of a fast recovery time for patients.
format Online
Article
Text
id pubmed-10055987
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100559872023-03-30 Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells Fernandes, Célio Júnior da C. da Silva, Rodrigo A. Foganholi Wood, Patrícia F. Ferreira, Marcel Rodrigues de Almeida, Gerson S. de Moraes, Julia Ferreira Bezerra, Fábio J. Zambuzzi, Willian F. J Funct Biomater Article It is important to understand whether endothelial cells are epigenetically affected by titanium-enriched media when angiogenesis is required during bone development and it is expected to be recapitulated during osseointegration of biomaterials. To better address this issue, titanium-enriched medium was obtained from incubation of titanium discs for up to 24 h as recommended by ISO 10993-5:2016, and further used to expose human umbilical vein endothelial cells (HUVECs) for up to 72 h, when the samples were properly harvested to allow molecular analysis and epigenetics. In general, our data show an important repertoire of epigenetic players in endothelial cells responding to titanium, reinforcing protein related to the metabolism of acetyl and methyl groups, as follows: Histone deacetylases (HDACs) and NAD-dependent deacetylase sirtuin-1 (Sirt1), DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) methylcytosine dioxygenases, which in conjunction culminate in driving chromatin condensation and the methylation profile of DNA strands, respectively. Taking our data into consideration, HDAC6 emerges as important player of this environment-induced epigenetic mechanism in endothelial cells, while Sirt1 is required in response to stimulation of reactive oxygen species (ROS) production, as its modulation is relevant to vasculature surrounding implanted devices. Collectively, all these findings support the hypothesis that titanium keeps the surrounding microenvironment dynamically active and so affects the performance of endothelial cells by modulating epigenetics. Specifically, this study shows the relevance of HDAC6 as a player in this process, possibly correlated with the cytoskeleton rearrangement of those cells. Furthermore, as those enzymes are druggable, it opens new perspectives to consider the use of small molecules to modulate their activities as a biotechnological tool in order to improve angiogenesis and accelerate bone growth with benefits of a fast recovery time for patients. MDPI 2023-02-27 /pmc/articles/PMC10055987/ /pubmed/36976055 http://dx.doi.org/10.3390/jfb14030131 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fernandes, Célio Júnior da C.
da Silva, Rodrigo A. Foganholi
Wood, Patrícia F.
Ferreira, Marcel Rodrigues
de Almeida, Gerson S.
de Moraes, Julia Ferreira
Bezerra, Fábio J.
Zambuzzi, Willian F.
Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
title Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
title_full Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
title_fullStr Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
title_full_unstemmed Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
title_short Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
title_sort titanium-enriched medium promotes environment-induced epigenetic machinery changes in human endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055987/
https://www.ncbi.nlm.nih.gov/pubmed/36976055
http://dx.doi.org/10.3390/jfb14030131
work_keys_str_mv AT fernandesceliojuniordac titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT dasilvarodrigoafoganholi titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT woodpatriciaf titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT ferreiramarcelrodrigues titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT dealmeidagersons titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT demoraesjuliaferreira titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT bezerrafabioj titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells
AT zambuzziwillianf titaniumenrichedmediumpromotesenvironmentinducedepigeneticmachinerychangesinhumanendothelialcells