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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

PI3K/AKT signaling drives titanium-induced angiogenic stimulus

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Author(s):
Martins, Bruna Rodrigues [1] ; Pinto, Thais Silva [1] ; da Costa Fernandes, Celio Junior [1] ; Bezerra, Fabio [1] ; Zambuzzi, Willian Fernando [1]
Total Authors: 5
Affiliation:
[1] UNESP Sao Paulo State Univ, Dept Chem & Biol Sci, Inst Biosci Botucatu, Botucatu, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE; v. 32, n. 1 JAN 27 2021.
Web of Science Citations: 0
Abstract

Although osseointegration and clinical success of titanium (Ti)-implanted materials depend on neovascularization in the reactional peri-implant tissue, very little has been achieved considering the Ti-molecules release on the behavior of endothelial cells. To address this issue, we challenged endothelial cells (HUVECs) with Ti-enriched medium obtained from two types of commercial titanium surfaces {[}presenting or not dual-acid etching (DAE)] up to 72h to allow molecular machinery analysis. Our data show that the Ti-enriched medium provokes significant stimulus of angiogenesis-related machinery in endothelial cells by upexpressing VEGFR1, VEGFR2, VEGF, eNOS, and iNOS genes, while the PI3K/Akt signaling pathway was also significantly enhanced. As PI3K/AKT signaling was related to angiogenesis in response to vascular endothelial growth factor (VEGF), we addressed the importance of PI3K/Akt upon Ti-enriched medium responses by concomitantly treating the cells with wortmannin, a well-known PI3K inhibitor. Wortmannin suppressed the angiogenic factors, because VEGF, VEGFR1, and eNOS genes were downregulated in those cells, highlighting the importance of PI3K/AKT signaling on driving angiogenic phenotype and angiogenesis performance within the peri-implant tissue reaction. In conjunction, these data reinforce that titanium-implantable devices modify the metabolism of surrounding cells, such as endothelial cells, probably coupling osteogenesis and angiogenesis processes in peri-implant tissue and then contributing to successfully osseointegration of biomedical titanium-based devices. (AU)

FAPESP's process: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
Grantee:Willian Fernando Zambuzzi
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 19/09140-6 - Titanium-enriched medium in shear-stressed endothelial cells: look on cell adhesion, survival and angiogenesis
Grantee:Bruna Rodrigues Martins
Support Opportunities: Scholarships in Brazil - Scientific Initiation