Zirconia stimulates ECM-remodeling as a prerequisite to pre-osteoblast adhesion/proliferation by possible interference with cellular anchorage

Author(s)

da Costa Fernandes, Celio J. ^[1] ; Ferreira, Marcel Rodrigues ^[1] ; Bezerra, Fabio J. B. ^[1] ; Zambuzzi, Willian F. ^[1]

Affiliation

^[1] Univ Estadual Paulista UNESP, Biosci Inst, Dept Chem & Biochem, Bioassays & Cell Dynam Lab, Botucatu, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE; v. 29, n. 4 APR 2018.
• Web of Science Citations: 4

Abstract

The biological response to zirconia (ZrO2) is not completely understood, which prompted us to address its effect on pre-osteoblastic cells in both direct and indirect manner. Our results showed that zirconia triggers important intracellular signaling mainly by governing survival signals which leads to cell adhesion and proliferation by modulating signaling cascade responsible for dynamic cytoskeleton rearrangement, as observed by fluorescence microscopy. The phosphorylations of Focal Adhesion Kinase (FAK) and Rac1 decreased in response to ZrO2 enriched medium. This corroborates the result of the crystal violet assay, which indicated a significant decrease of pre-osteoblast adhesion in responding to ZrO2 enriched medium. However, we credit this decrease on pre-osteoblast adhesion to the need to govern intracellular repertory of intracellular pathways involved with cell cycle progression, because we found a significant up-phosphorylation of Mitogen-Activated Protein Kinase (MAPK)-p38 and Cyclin-dependent kinase 2 (CDK2), while p15 (a cell cycle suppressor) decreased. Importantly, Protein phosphatase 2 A (PP2A) activity decreased, guaranteeing the significant up-phosphorylation of MAPK-p38 in response to ZrO2 enriched medium. Complementarily, there was a regulation of Matrix Metalloproteinases (MMPs) in response to Zirconia and this remodeling could affect cell phenotype by interfering on cell anchorage. Altogether, our results show a repertory of signaling molecules, which suggests that ECM remodel as a pre-requisite to pre-osteoblast phenotype by affecting their anchoring in responding to zirconia. (AU)

• FAPESP's process: 15/03639-8 - Global signal transduction involved in the immediate response to the two surfaces of titanium alloys: building OsteoBLAST database
• Grantee: Marcel Rodrigues Ferreira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Willian Fernando Zambuzzi
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/08888-9 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Célio Junior da Costa Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)