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    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 β-catenin demonstrated that Fzd6 disruption inhibited the osteoblast differentiation induced by Ti-Nano by preventing the activation of Wnt/β-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/β-catenin signaling and the cellular mechanisms modulated by nanotopography during osteoblast differentiation. © 2020 Wiley Periodicals, Inc.


    Rodrigo Paolo Flores Abuna, Fabiola Singaretti Oliveira, Leticia Faustino Adolpho, Roger Rodrigo Fernandes, Adalberto Luiz Rosa, Marcio Mateus Beloti. Frizzled 6 disruption suppresses osteoblast differentiation induced by nanotopography through the canonical Wnt signaling pathway. Journal of cellular physiology. 2020 Nov;235(11):8293-8303

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    PMID: 32239701

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