PI3K/AKT signaling drives titanium-induced angiogenic stimulus

Autor(es)

Martins, Bruna Rodrigues ^[1] ; Pinto, Thais Silva ^[1] ; da Costa Fernandes, Celio Junior ^[1] ; Bezerra, Fabio ^[1] ; Zambuzzi, Willian Fernando ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Sao Paulo State Univ, Dept Chem & Biol Sci, Inst Biosci Botucatu, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE; v. 32, n. 1 JAN 27 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/09140-6 - Efeito do meio enriquecido com titânio no comportamento de células endoteliais submetidas ao modelo de shear-stress: análise de vias de adesão, sobrevivência e angiogênese
• Beneficiário: Bruna Rodrigues Martins
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica