Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography
Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | https://www.mdpi.com/2079-4983/14/2/79 |
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| author | Paola Gomes Souza Leticia Faustino Adolpho Helena Bacha Lopes Denise Weffort Alann Thaffarell Portilho Souza Fabiola Singaretti Oliveira Adalberto Luiz Rosa Marcio Mateus Beloti |
| author_facet | Paola Gomes Souza Leticia Faustino Adolpho Helena Bacha Lopes Denise Weffort Alann Thaffarell Portilho Souza Fabiola Singaretti Oliveira Adalberto Luiz Rosa Marcio Mateus Beloti |
| author_sort | Paola Gomes Souza |
| collection | DOAJ |
| description | Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H<sub>2</sub>SO<sub>4</sub>/H<sub>2</sub>O<sub>2</sub>. Methods: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene. Osteoblast differentiation was evaluated by alkaline phosphatase activity and mineralization, and the expression of Hedgehog and Notch receptors was also evaluated. Results: In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more prominent effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effects on osteoblast differentiation that was more intense on Ti-Nano. Conclusion: Our results indicated that the Hedgehog and Notch signalling pathways drive osteoblast/Ti interactions more intensely on nanotopography. We also demonstrated that combining Hedgehog activation with Notch inhibition exhibits synergistic effects on osteoblast differentiation, especially on Ti-Nano. The uncovering of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces. |
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| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-11T08:37:07Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Journal of Functional Biomaterials |
| spelling | doaj.art-8eaa05e1a15b49538ff8045d72cf7cb52023-11-16T21:24:22ZengMDPI AGJournal of Functional Biomaterials2079-49832023-01-011427910.3390/jfb14020079Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with NanotopographyPaola Gomes Souza0Leticia Faustino Adolpho1Helena Bacha Lopes2Denise Weffort3Alann Thaffarell Portilho Souza4Fabiola Singaretti Oliveira5Adalberto Luiz Rosa6Marcio Mateus Beloti7Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, BrazilBackground: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H<sub>2</sub>SO<sub>4</sub>/H<sub>2</sub>O<sub>2</sub>. Methods: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene. Osteoblast differentiation was evaluated by alkaline phosphatase activity and mineralization, and the expression of Hedgehog and Notch receptors was also evaluated. Results: In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more prominent effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effects on osteoblast differentiation that was more intense on Ti-Nano. Conclusion: Our results indicated that the Hedgehog and Notch signalling pathways drive osteoblast/Ti interactions more intensely on nanotopography. We also demonstrated that combining Hedgehog activation with Notch inhibition exhibits synergistic effects on osteoblast differentiation, especially on Ti-Nano. The uncovering of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces.https://www.mdpi.com/2079-4983/14/2/79hedgehognanotopographynotchosteoblasttitanium |
| spellingShingle | Paola Gomes Souza Leticia Faustino Adolpho Helena Bacha Lopes Denise Weffort Alann Thaffarell Portilho Souza Fabiola Singaretti Oliveira Adalberto Luiz Rosa Marcio Mateus Beloti Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography Journal of Functional Biomaterials hedgehog nanotopography notch osteoblast titanium |
| title | Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography |
| title_full | Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography |
| title_fullStr | Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography |
| title_full_unstemmed | Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography |
| title_short | Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography |
| title_sort | effects of modulation of the hedgehog and notch signaling pathways on osteoblast differentiation induced by titanium with nanotopography |
| topic | hedgehog nanotopography notch osteoblast titanium |
| url | https://www.mdpi.com/2079-4983/14/2/79 |
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