Participation of hedgehog and notch signaling pathways in titanium surface induced osteoblast differentiation with nanotopography

Author(s)

Paola Gomes Souza

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC)
• Defense date: 2023-01-06

Examining board members

Márcio Mateus Beloti; Karen Renata Nakamura Hiraki; Luciano José Pereira; Mauro Pedrine Santamaria

• Advisor: Márcio Mateus Beloti; Adalberto Luiz Rosa

Abstract

The Hedgehog and Notch signaling pathways affect osteogenesis and can drive the osteoblast/titanium (Ti) interactions. We investigated the effect of the modulation of these signaling on osteoblast differentiation induced by the nanostructured Ti (Ti-Nano) generated by H2SO4/H2O2. Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of agonist purmorphamine or antagonist cyclopamine of the Hedgehog pathway and antagonist DAPT or agonist bexarotene of the Notch pathway. Osteoblast differentiation was evaluated by the expression of bone markers, alkaline phosphatase activity and mineralization and the expression of Hedgehog and Notch receptors. In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more pronounced effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effect on osteoblast differentiation that was more intense on Ti-Nano. Our results indicate that the Hedgehog and Notch signaling pathways drive osteoblast/Ti interactions, with more pronounced effects on nanotopography. We also demonstrated that the combination of Hedgehog activation with Notch inhibition exhibits synergistic effect on osteoblast differentiation, especially on Ti-Nano. The uncover of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces. (AU)

• FAPESP's process: 19/15531-8 - Participation of Hedgehog and Notch signaling pathways in the osteoblastic differentiation induced by titanium with nanotopography
• Grantee: Paola Gomes Souza
• Support Opportunities: Scholarships in Brazil - Doctorate