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Frizzled 6 disruption suppresses osteoblast differentiation induced by nanotopography through the canonical Wnt signaling pathway

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Autor(es):
Flores Abuna, Rodrigo Paolo ; Oliveira, Fabiola Singaretti ; Adolpho, Leticia Faustino ; Fernandes, Roger Rodrigo ; Rosa, Adalberto Luiz ; Beloti, Marcio Mateus
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Physiology; v. 235, n. 11, p. 11-pg., 2020-04-02.
Resumo

This study aimed to investigate if wingless-related integration site (Wnt) signaling participates in the high osteogenic potential of titanium with nanotopography (Ti-Nano). We showed that among the several components of the Wnt signaling pathway, Frizzled 6 (Fzd6) was the transcript most intensely modulated by nanotopography compared with the untreated Ti surface (Ti-Machined). Then, we investigated whether and how Fzd6 participates in the regulation of osteoblast differentiation caused by nanotopography. The Fzd6 silencing with CRISPR-Cas9 transfection in MC3T3-E1 cells induced a more pronounced inhibition of osteoblast differentiation of cells cultured on nanotopography than those cultured on Ti-Machined. The analysis of the expression of calcium-calmodulin-dependent protein kinase II and beta-catenin demonstrated that Fzd6 disruption inhibited the osteoblast differentiation induced by Ti-Nano by preventing the activation of Wnt/beta-catenin but not that of Wnt/Ca2+ signaling, which is usually triggered by the receptor Fzd6. These findings elucidate the biological function of Fzd6 as a receptor that triggers Wnt/beta-catenin signaling and the cellular mechanisms modulated by nanotopography during osteoblast differentiation. (AU)

Processo FAPESP: 16/14171-0 - Papel das Vias de Sinalização de Wnt no Potencial Osteogênico de Superfície de Titânio com Nanotopografia
Beneficiário:Márcio Mateus Beloti
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/17356-6 - Efeito da Superfície de Titânio com Nanotopografia sobre a Interação entre Osteoblastos e Osteoclastos
Beneficiário:Márcio Mateus Beloti
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/14711-4 - Papel das Vias de Sinalização de Wnt no Potencial Osteogênico de Superfície de Titânio com Nanotopografia
Beneficiário:Rodrigo Paolo Flores Abuna
Modalidade de apoio: Bolsas no Brasil - Doutorado