Effect of a hypoxia model on angiogenesis-osteogenesis coupling: a special look at micro vesicles and potential biotechnological applications

• Grant number: 19/26854-2
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2020 - March 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Willian Fernando Zambuzzi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

With increasing concern about the life expectancy of the population, regenerative processes of bone tissue have been urgently considered by emerging countries. Currently, it is shown that the growth of blood vessels in the bone is associated with osteogenesis, and little has been explored in the elaboration of biotechnological processes on this matter. Another important point at this conjuncture is the high demand for angiogenesis in the state of tissue hypoxia. Thus, knowing the in-depth way or involvement of hypoxia, coordinating this coupling represents an extremely important step in the search for more efficient therapies. In recent years, with the support of FAPESP (JP-2014 / 22689-3), we have expanded our understanding of the issues related to this type of crosstalk between endothelial and bone cells, where emphasis is given to extracellular microvesicles. Thus, our idea is inducing a hypoxic state in endothelial and smooth muscle cells by using well-known hypoxiant element, CoCl2, a chemical model of hypoxia. In this model, also, the cells will be subjected to a shear stress circuit, mimicking blood flow. In order to better understand the role of microvesicles in the coupling of angiogenesis and osteogenesis in a hypoxic environment, we specifically intend to: 1. Evaluate the cytotoxicity of CoCl2 in endothelial, muscle and osteogenic cells; 2. Subject endothelial and smooth muscle cells to the stress differential shear stress model (normo-, hyper- and hypotension) in the presence and / or absence of CoCl2; 3. Investigate epigenetic mechanisms involved with activation of angiogenic genes and HIF1±; 4. Harvest the conditioned medium and verify its osteogenic potential using undifferentiated cells; 5. Harvest and characterize microvesicles released by endothelial and smooth muscle cells, whether in hypoxic or not; 6. Concentrate these MVs and challenge undifferentiated cells in order to validate (or not) their osteogenic potential. Finally, we intend that this new routine can gather impact information in scientific articles and patents, in addition to acquiring knowledge about related methodologies, not yet practiced at the Chemical and Biochemical Department, IBB-UNESP, through qualification of human resources. The proposed project will use structural investment acquired by JP-FAPESP (2014 / 22689-3). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, MARCEL RODRIGUES; ZAMBUZZI, WILLIAN FERNANDO. Platelet microparticles load a repertory of miRNAs programmed to drive osteogenic phenotype. Journal of Biomedical Materials Research Part A, v. 109, n. 8, p. 1502-1511, AUG 2021. (14/22689-3, 19/26854-2, 18/05731-7)

DA COSTA FERNANDES, CELIO JUNIOR; DE ALMEIDA, GERSON SANTOS; PINTO, THAIS SILVA; TEIXEIRA, SUELEN APARECIDA; BEZERRA, FABIO J.; ZAMBUZZI, WILLIAN FERNANDO. Metabolic effects of CoCr-enriched medium on shear-stressed endothelial cell and osteoblasts: A possible mechanism involving a hypoxic condition on bone healing. Materials Science & Engineering C-Materials for Biological Applications, v. 128, SEP 2021. (19/26854-2)

FERNANDES, CELIO JUNIOR DA C.; DA SILVA, RODRIGO A.; WOOD, PATRICIA FRETES; TEIXEIRA, SUELEN APARECIDA; BEZERRA, FABIO; ZAMBUZZI, WILLIAN F.. The molecular pathway triggered by zirconia in endothelial cells involves epigenetic control. TISSUE & CELL, v. 73, DEC 2021. (19/26854-2)