Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/jfb14030131 http://hdl.handle.net/11449/247066 |
Resumo: | 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. |
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Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cellsangiogenesisbiological analysisbiomaterialendothelial cellepigenetictitaniumIt 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.Laboratory of Bioassays and Cellular Dynamics Department of Chemical and Biological Sciences Institute of Biosciences UNESP—São Paulo State University, SPDepartment of Dentistry University of Taubaté, SPProgram in Environmental and Experimental Pathology Paulista University, SPLaboratory of Bioassays and Cellular Dynamics Department of Chemical and Biological Sciences Institute of Biosciences UNESP—São Paulo State University, SPUniversidade Estadual Paulista (UNESP)University of TaubatéPaulista UniversityFernandes, Célio Júnior da C. [UNESP]da Silva, Rodrigo A. FoganholiWood, Patrícia F. [UNESP]Ferreira, Marcel Rodrigues [UNESP]de Almeida, Gerson S. [UNESP]de Moraes, Julia Ferreira [UNESP]Bezerra, Fábio J. [UNESP]Zambuzzi, Willian F. [UNESP]2023-07-29T12:58:09Z2023-07-29T12:58:09Z2023-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/jfb14030131Journal of Functional Biomaterials, v. 14, n. 3, 2023.2079-4983http://hdl.handle.net/11449/24706610.3390/jfb140301312-s2.0-85151148643Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Functional Biomaterialsinfo:eu-repo/semantics/openAccess2023-07-29T12:58:09Zoai:repositorio.unesp.br:11449/247066Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-07-29T12:58:09Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells Fernandes, Célio Júnior da C. [UNESP] angiogenesis biological analysis biomaterial endothelial cell epigenetic titanium |
title_short |
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_sort |
Titanium-Enriched Medium Promotes Environment-Induced Epigenetic Machinery Changes in Human Endothelial Cells |
author |
Fernandes, Célio Júnior da C. [UNESP] |
author_facet |
Fernandes, Célio Júnior da C. [UNESP] da Silva, Rodrigo A. Foganholi Wood, Patrícia F. [UNESP] Ferreira, Marcel Rodrigues [UNESP] de Almeida, Gerson S. [UNESP] de Moraes, Julia Ferreira [UNESP] Bezerra, Fábio J. [UNESP] Zambuzzi, Willian F. [UNESP] |
author_role |
author |
author2 |
da Silva, Rodrigo A. Foganholi Wood, Patrícia F. [UNESP] Ferreira, Marcel Rodrigues [UNESP] de Almeida, Gerson S. [UNESP] de Moraes, Julia Ferreira [UNESP] Bezerra, Fábio J. [UNESP] Zambuzzi, Willian F. [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) University of Taubaté Paulista University |
dc.contributor.author.fl_str_mv |
Fernandes, Célio Júnior da C. [UNESP] da Silva, Rodrigo A. Foganholi Wood, Patrícia F. [UNESP] Ferreira, Marcel Rodrigues [UNESP] de Almeida, Gerson S. [UNESP] de Moraes, Julia Ferreira [UNESP] Bezerra, Fábio J. [UNESP] Zambuzzi, Willian F. [UNESP] |
dc.subject.por.fl_str_mv |
angiogenesis biological analysis biomaterial endothelial cell epigenetic titanium |
topic |
angiogenesis biological analysis biomaterial endothelial cell epigenetic titanium |
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. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T12:58:09Z 2023-07-29T12:58:09Z 2023-03-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/jfb14030131 Journal of Functional Biomaterials, v. 14, n. 3, 2023. 2079-4983 http://hdl.handle.net/11449/247066 10.3390/jfb14030131 2-s2.0-85151148643 |
url |
http://dx.doi.org/10.3390/jfb14030131 http://hdl.handle.net/11449/247066 |
identifier_str_mv |
Journal of Functional Biomaterials, v. 14, n. 3, 2023. 2079-4983 10.3390/jfb14030131 2-s2.0-85151148643 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Functional Biomaterials |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965574076301312 |