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Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration

Grant number: 14/22689-3
Support type:Research Grants - Young Investigators Grants
Duration: December 01, 2015 - November 30, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Willian Fernando Zambuzzi
Grantee:Willian Fernando Zambuzzi
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):19/09735-0 - BONEInk: synthesis and characterization of chitosan crosslinked with carbon nanotubes modified with RGD peptides and HA crystals for potential application of bioimpression of bone tissue, BP.DR
19/09943-1 - Molecular signatures of mesenchymal stem cell transcriptome from adipose tissue in differentiation mechanism: a special look for inflammation, BP.IC
19/09140-6 - Titanium-enriched medium in shear-stressed endothelial cells: look on cell adhesion, survival and angiogenesis, BP.IC
+ associated scholarships 19/04495-0 - The role of T3 hormone on LCN2 expression and their contribution on appetite, BP.MS
18/05731-7 - Lyophilized PRP associated with nano-hydroxyapatite in cell performance and bone regeneration, BP.DR
17/18349-0 - Endothelial cell behavior under arterial hypertension in vitro and its impact on osteogenesis, BP.MS
16/20505-8 - Endothelial tissue spheroids: acquisition, charactherization and their osteopromotor potential, BP.MS
16/22270-8 - Behavior of endothelial and smooth muscular cells under shear-stress model: a panorama of cellular, ultrastructural and biochemistry aspects, BP.MS
16/10392-1 - Osteopromotor effect of " 3,3 ', 5 triiodo - L- thyronine " associate to trophic factors produced by endothelial cells, BP.IC
16/08888-9 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration, BP.DD
16/01139-0 - Epigenetic modulation triggered by paracrine factors from endothelial cells on osteoblast, BP.PD - associated scholarships

Abstract

The mammals skeletal system contains a collection of cells, in a hierarchical manner, maintain bone formation throughout life. In this context, we know that osteogenesis is essential for bone deposition, as well as fracture healing through regenerative mechanisms; in addition, we know these processes often decrease with the progress of age, leading to bone loss and an increased incidence of fractures. Currently, bone defects constitute a public health problem since the life expectancy of the population has increased significantly over the last years. "Rebuild" the lost tissue is one of the great challenges of surgeons in the area, often requiring the application of a biomaterial that allows functional repair of the lost tissue. Despite its medical, social and economic importance, little progress has been made regarding the bioassay methodologies able to rank new therapies. We now know that the bone development is a complex event and orchestrated by intercellular signaling as it has been shown by Prof. RH Adams, from Max Planck Institute for Molecular Biomedicine, recently published in Nature. These works justify our interest in studying the crosstalk between the osteogenic and endothelial lineages, emphasizing the importance of knowing the repertoire of molecules secreted by osteoblasts and endothelial cells during bone remodeling. In this context, we will investigate: 1. The interplay between bone and endothelial cells - evaluating vesicles secreted and extracellular proteins in this context; 2. Characterization of a functional blood vessel tissue equivalent and its impact on osteoblasts and osteoclasts; 3. Check through the biomarkers listed in previous step, its conservation during the intramembranous and endochondral embryonic development; 4. The angiogenic-coupled osteogenesis during tissue regeneration of the alveolar bone; In this project, we celebrate the participation of international researchers such as: Prof. Anna Teti (Italy, expert in bone cell energy metabolism and molecular characteristics which determine the phenotype of osteoblasts, osteoclasts and osteocytes), Professor Hans van Leeuwen (Netherlands, expert in microvesicles extracellular analysis) and Prof. Suvro Chartjee (India, expert in endothelial cells, Shear stress and NO signaling). This assembly of international researchers is the result of INTERBONE, Consorcium that Prof. William Zambuzzi (proponent of this project) integrates as principal investigator since 2011. Thus, among the expected outcomes for this project include: 1. Implementation in the IBB - UNESP, research on mineralized tissues, with multi-user equipment capable of attend this community; 2. Multidisciplinary; 3. Maintenance of national and international partnerships, contributing to exchanges and training of our undergraduate and graduate students; 4. Contribution with results that can be explored in the context of applied research. (AU)

Scientific publications (26)
(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)
DA COSTA FERNANDES, CELIO JR.; VEIGA, MARIANA R.; SERRAO PERACOLI, MARIA TEREZINHA; ZAMBUZZI, WILLIAN F. Modulatory effects of silibinin in cell behavior during osteogenic phenotype. Journal of Cellular Biochemistry, v. 120, n. 8, p. 13413-13425, AUG 2019. Web of Science Citations: 0.
DA SILVA, RODRIGO A.; FUHLER, GWENNY M.; JANMAAT, VINCENT T.; FERNANDES, CELLO JUNIOR DA C.; FELTRAN, GEORGIA DA SILVA; OLIVEIRA, FLAVIA AMADEU; MATOS, ADRIANA ARRUDA; OLIVEIRA, RODRIGO CARDOSO; FERREIRA, MARCEL RODRIGUES; ZAMBUZZI, WILLIAN F.; PEPPELENBOSCH, MAIKEL P. HOXA cluster gene expression during osteoblast differentiation involves epigenetic control. BONE, v. 125, p. 74-86, AUG 2019. Web of Science Citations: 1.
FELTRAN, GEORGIA DA S.; BEZERRA, FABIO; DA COSTA FERNANDES, CELIO JUNIOR; FERREIRA, MARCEL RODRIGUES; ZAMBUZZI, WILLIAN F. Differential inflammatory landscape stimulus during titanium surfaces obtained osteogenic phenotype. Journal of Biomedical Materials Research Part A, v. 107, n. 8, p. 1597-1604, AUG 2019. Web of Science Citations: 1.
FERNANDES, CELIO JR DA COSTA; PINTO, THAIS SILVA; KANG, HA RAM; PADILHA, PEDRO DE MAGALHAES; KOH, IVAN HONG JUN; LEOPOLDO CONSTANTINO, VERA REGINA; ZAMBUZZI, WILLIAN F. Layered Double Hydroxides Are Promising Nanomaterials for Tissue Bioengineering Application. ADVANCED BIOSYSTEMS, v. 3, n. 7 JUL 2019. Web of Science Citations: 1.
PINTO, THAIS SILVA; DA COSTA FERNANDES, CELIO JUNIOR; DA SILVA, RODRIGO AUGUSTO; GOMES, ANDERSON MOREIRA; SOUZA VIEIRA, JOSE CAVALCANTE; PADILHA, PEDRO DE M.; ZAMBUZZI, WILLIAN F. c-Src kinase contributes on endothelial cells mechanotransduction in a heat shock protein 70-dependent turnover manner. Journal of Cellular Physiology, v. 234, n. 7, p. 11287-11303, JUL 2019. Web of Science Citations: 1.
DA SILVA, RODRIGO A.; FERNANDES, CELIO JR DA C.; FELTRAN, GEORGIA DA S.; GOMES, ANDERSON M.; DE CAMARGO ANDRADE, AMANDA FANTINI; ANDIA, DENISE C.; PEPPELENBOSCH, MAIKEL P.; ZAMBUZZI, WILLIAN F. Laminar shear stress-provoked cytoskeletal changes are mediated by epigenetic reprogramming of TIMP1 in human primary smooth muscle cells. Journal of Cellular Physiology, v. 234, n. 5, p. 6382-6396, MAY 2019. Web of Science Citations: 2.
BENELLI FRANCISCO, VALESCA CRISTIANE; OKINO-DELGADO, CLARISSA HAMAIO; ZANUTTO ELGUI, MIRELLA R.; DA COSTA FERNANDES, CELIO JUNIOR; FACANALI, ROSELAINE; DA SILVA, RODRIGO AUGUSTO; ZAMBUZZI, WILLIAN FERNANDO; MAYO MARQUES, MARCIA ORTIZ; FLEURI, LUCIANA FRANCISCO. Plant oil bioconversion into increase biological activity through lipases derived from wastes. INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY, v. 54, n. 4, SI, p. 1089-1099, APR 2019. Web of Science Citations: 0.
SARTORETTO, SUELEN; GEMINI-PIPERNI, SARA; DA SILVA, RODRIGO A.; CALASANS, MONICA D.; RUCCI, NADIA; PIRES DOS SANTOS, THAIS M.; LIMA, INAYA B. C.; ROSSI, ALEXANDRE M.; ALVES, GUTEMBERG; GRANJEIRO, JOSE M.; TETI, ANNA; ZAMBUZZI, WILLIAN F. Apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) contributes to osteoblast differentiation and osteogenesis. Journal of Cellular Physiology, v. 234, n. 4, p. 4140-4153, APR 2019. Web of Science Citations: 0.
BARONCELLI, MARTA; FUHLER, GWENNY M.; VAN DE PEPPEL, JEROEN; ZAMBUZZI, WILLIAN F.; VAN LEEUWEN, JOHANNES P.; VAN DER EERDEN, BRAM C. J.; PEPPELENBOSCH, MAIKEL P. Human mesenchymal stromal cells in adhesion to cell-derived extracellular matrix and titanium: Comparative kinome profile analysis. Journal of Cellular Physiology, v. 234, n. 3, p. 2984-2996, MAR 2019. Web of Science Citations: 1.
FELTRAN, GEORGIA DA SILVA; DA COSTA FERNANDES, CELIO JUNIOR; FERREIRA, MARCEL RODRIGUES; KANG, HA RAM; DE CARVALHO BOVOLATO, ANA LIVIA; GOLIM, MARJORIE DE ASSIS; DEFFUNE, ELENICE; JUN KOH, IVAN HONG; LEOPOLDO CONSTANTINO, VERA REGINA; ZAMBUZZI, WILLIAN F. Sonic hedgehog drives layered double hydroxides-induced acute inflammatory landscape. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 174, p. 467-475, FEB 1 2019. Web of Science Citations: 2.
CINTIA KAZUKO TOKUHARA; MARIANA RODRIGUES SANTESSO; GABRIELA SILVA NEUBERN DE OLIVEIRA; TALITA MENDES DA SILVA VENTURA; JULIO TOSHIMI DOYAMA; WILLIAN FERNANDO ZAMBUZZI; RODRIGO CARDOSO DE OLIVEIRA. Updating the role of matrix metalloproteinases in mineralized tissue and related diseases. Journal of Applied Oral Science, v. 27, p. -, 2019. Web of Science Citations: 0.
DA SILVA, RODRIGO A.; DE CAMARGO ANDRADE, AMANDA FANTINI; FELTRAN, GEORGIA DA SILVA; FERNANDES, CELLO JUNIOR DA C.; DE ASSIS, RAHYZA INACIO F.; FERREIRA, MARCEL RODRIGUES; ANDIA, DENISE C.; ZAMBUZZI, WILLIAN F. The role of triiodothyronine hormone and mechanically-stressed endothelial cell paracrine signalling synergism in gene reprogramming during hBMSC-stimulated osteogenic phenotype in vitro. Molecular and Cellular Endocrinology, v. 478, p. 151-167, DEC 15 2018. Web of Science Citations: 3.
CORREA, D. R. N.; KURODA, P. A. B.; LOURENCO, M. L.; BUZALAF, M. A. R.; MENDOZA, M. E.; ARCHANJO, B. S.; ACHETE, C. A.; ROCHA, L. A.; GRANDINI, C. R. Microstructure and selected mechanical properties of aged Ti-15Zr-based alloys for biomedical applications. Materials Science & Engineering C-Materials for Biological Applications, v. 91, p. 762-771, OCT 1 2018. Web of Science Citations: 3.
CORREA, D. R. N.; KURODA, P. A. B.; LOURENCO, M. L.; FERNANDES, C. J. C.; BUZALAF, M. A. R.; ZAMBUZZI, W. F.; GRANDINI, C. R. Development of Ti-15Zr-Mo alloys for applying as implantable biomedical devices. Journal of Alloys and Compounds, v. 749, p. 163-171, JUN 15 2018. Web of Science Citations: 9.
DA COSTA FERNANDES, CELIO J.; FERREIRA, MARCEL RODRIGUES; BEZERRA, FABIO J. B.; ZAMBUZZI, WILLIAN F. Zirconia stimulates ECM-remodeling as a prerequisite to pre-osteoblast adhesion/proliferation by possible interference with cellular anchorage. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, v. 29, n. 4 APR 2018. Web of Science Citations: 3.
FERNANDES, CELIO J. C.; BEZERRA, FABIO; FERREIRA, MARCEL R.; ANDRADE, AMANDA F. C.; PINTO, THAIS SILVA; ZAMBUZZI, WILLIAN F. Nano hydroxyapatite-blasted titanium surface creates a biointerface able to govern Src-dependent osteoblast metabolism as prerequisite to ECM remodeling. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 163, p. 321-328, MAR 1 2018. Web of Science Citations: 7.
FERNANDES, CELIO J. C.; BEZERRA, FABIO; DO CARMO, MAIARA DAS D.; FELTRAN, GEORGIA S.; ROSSI, MARIANA C.; DA SILVA, RODRIGO A.; PADILHA, PEDRO DE M.; ZAMBUZZI, WILLIAN F. CoCr-enriched medium modulates integrin-based downstream signaling and requires a set of inflammatory genes reprograming in vitro. Journal of Biomedical Materials Research Part A, v. 106, n. 3, p. 839-849, MAR 2018. Web of Science Citations: 4.
KANG, HA RAM; DA COSTA FERNANDES, CELIO JUNIOR; DA SILVA, RODRIGO AUGUSTO; LEOPOLDO CONSTANTINO, VERA REGINA; JUN KOH, IVAN HONG; ZAMBUZZI, WILLIAN F. Mg-Al and Zn-Al Layered Double Hydroxides Promote Dynamic Expression of Marker Genes in Osteogenic Differentiation by Modulating Mitogen-Activated Protein Kinases. ADVANCED HEALTHCARE MATERIALS, v. 7, n. 4 FEB 21 2018. Web of Science Citations: 7.
ATHANAZIO-HELIODORO, JULIA CAROLINA; OKINO-DELGADO, CLARISSA HAMAIO; DA COSTA FERNANDES, CELIO JUNIOR; ZANUTTO, MIRELLA ROSSITTO; DO PRADO, DEBORA ZANONI; DA SILVA, RODRIGO AUGUSTO; FACANALI, ROSELAINE; ZAMBUZZI, WILLIAN FERNANDO; MAYO MARQUES, MARCIA ORTIZ; FLEURI, LUCIANA FRANCISCO. Improvement of lipase obtaining system by orange waste-based solid-state fermentation: production, characterization and application. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 48, n. 7, p. 565-573, 2018. Web of Science Citations: 3.
DA COSTA FERNANDES, CELIO J.; BEZERRA, FABIO J. B.; SOUZA, BRUNO DE CAMPOS; CAMPOS, MONICA APARECIDA; ZAMBUZZI, WILLIAN FERNANDO. Titanium-enriched medium drives low profile of ECM remodeling as a pre-requisite to pre-osteoblast viability and proliferative phenotype. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, v. 50, p. 339-346, 2018. Web of Science Citations: 2.
NASCIMENTO, AUGUSTO S.; PERES, LUISA L.; FARI, ALESSANDRA V. S.; MILANI, RENATO; SILVA, RODRIGO A.; FERNANDES, JR., CELIO DA COSTA; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, CARMEN V.; ZAMBUZZI, WILLIAN F. Phosphoproteome profiling reveals critical role of JAK-STAT signaling in maintaining chemoresistance in breast cancer. ONCOTARGET, v. 8, n. 70, p. 114756-114768, DEC 29 2017. Web of Science Citations: 6.
DA COSTA FERNANDES, CELIO J.; DO NASCIMENTO, AUGUSTO SANTANA; DA SILVA, RODRIGO A.; ZAMBUZZI, WILLIAN F. Fibroblast contributes for osteoblastic phenotype in a MAPK-ERK and sonic hedgehog signaling-independent manner. Molecular and Cellular Biochemistry, v. 436, n. 1-2, p. 111-117, DEC 2017. Web of Science Citations: 8.
ROSSI, M. C.; BEZERRA, F. J. B.; SILVA, R. A.; CRULHAS, B. P.; FERNANDES, C. J. C.; NASCIMENTO, A. S.; PEDROSA, V. A.; PADILHA, P.; ZAMBUZZI, W. F. Titanium-released from dental implant enhances pre-osteoblast adhesion by ROS modulating crucial intracellular pathways. Journal of Biomedical Materials Research Part A, v. 105, n. 11, p. 2968-2976, NOV 2017. Web of Science Citations: 10.
OKINO-DELGADO, CLARISSA HAMAIO; DO PRADO, DEBORA ZANONI; FACANALI, ROSELAINE; ORTIZ MARQUES, MARCIA MAYO; NASCIMENTO, AUGUSTO SANTANA; DA COSTA FERNANDES, CELIO JUNIOR; ZAMBUZZI, WILLIAM FERNANDO; FLEURI, LUCIANA FRANCISCO. Bioremediation of cooking oil waste using lipases from wastes. PLoS One, v. 12, n. 10 OCT 26 2017. Web of Science Citations: 6.
MARUMOTO, ARIANE; MILANI, RENATO; DA SILVA, RODRIGO A.; DA COSTA FERNANDES, CELIO JUNIOR; GRANJEIRO, JOSE MAURO; FERREIRA, CARMEN V.; PEPPELENBOSCH, MAIKEL P.; ZAMBUZZI, WILLIAN F. Phosphoproteome analysis reveals a critical role for hedgehog signalling in osteoblast morphological transitions. BONE, v. 103, p. 55-63, OCT 2017. Web of Science Citations: 10.
BEZERRA, FABIO; FERREIRA, MARCEL R.; FONTES, GISELLE N.; DA COSTA FERNANDES, CELIO JR; ANDIA, DENISE C.; CRUZ, NILSON C.; DA SILVA, RODRIGO A.; ZAMBUZZI, WILLIAN F. Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by modulating critical intracellular pathways. Biotechnology and Bioengineering, v. 114, n. 8, p. 1888-1898, AUG 2017. Web of Science Citations: 16.

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