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

Author(s)

Flores Abuna, Rodrigo Paolo ; Oliveira, Fabiola Singaretti ; Adolpho, Leticia Faustino ; Fernandes, Roger Rodrigo ; Rosa, Adalberto Luiz ; Beloti, Marcio Mateus

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 235, n. 11, p. 11-pg., 2020-04-02.

Abstract

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)

• FAPESP's process: 16/14171-0 - Role of Wnt Signaling Pathways in the Osteogenic Potential of Titanium Surface with Nanotopography
• Grantee: Márcio Mateus Beloti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/17356-6 - Effect of titanium surface with nanotopography on the interaction between osteoblasts and osteoclasts
• Grantee: Márcio Mateus Beloti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/14711-4 - Role of Wnt Signaling Pathways in the Osteogenic Potential of Titanium Surface with Nanotopography
• Grantee: Rodrigo Paolo Flores Abuna
• Support Opportunities: Scholarships in Brazil - Doctorate