Epigenetic modulation triggered by paracrine factors from endothelial cells on osteoblast

• Grant number: 16/01139-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2016
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Rodrigo Augusto da Silva
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration, AP.JP
• Associated scholarship(s): 18/10443-0 - Endothelial-induced osteogenic phenotype: lessons from human iPSCs technology and epigenetic control, BE.EP.PD 17/01046-5 - secRNA and DNA-methylome of osteoblast cells in response to paracrine effects od endothelial cells under a static and dynamic model., BE.EP.PD

Abstract

The skeletal system of mammals contains a collection of cells, which in a hierarchical manner, maintain bone formation during the life. In this context, we know that osteogenesis is essential for bone renewal, as well as the bone healing through regenerative mechanisms; we know that 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 when the life expectancy of the population has increased significantly. Rebuilding 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 lost tissue. Despite its medical, social and economic importance, little progress has been made regarding methodologies able to elect new therapies. We now know that the development and bone regeneration is a complex event and orchestrated by paracrine mechanisms of intercellular signaling showing that osteogenesis is coupled to angiogenesis since from the elegant work led by Prof. R. H. Adams of the Max Planck Institute for Molecular Biomedicine, recently published in Nature. In this context, our project aims characterize epigenetic alterations triggered by paracrine factors produced by endothelial cells in osteoblastic cells. To note, this application is linked with a current financing project from FAPESP (JP: 2014 / 22689-3), where our objective is to map the repertoire of molecules secreted by osteoblasts and endothelial cells and identify their effects each other during bone remodeling. Thus, we are grateful with the interest from Dr. Rodrigo since he has skills on cell biology, microscopy and epigenetic field.

Scientific publications

(10)

(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 SILVA, RODRIGO A.; FERREIRA, MARCEL RODRIGUES; GOMES, ANDERSON MOREIRA; ZAMBUZZI, WILLIAN F.. LncRNA HOTAIR is a novel endothelial mechanosensitive gene. Journal of Cellular Physiology, OCT 2019. (16/01139-0, 14/22689-3)

JANMAAT, VINCENT T.; NESTERUK, KATERYNA; SPAANDER, MANON C. W.; VERHAAR, AUKE P.; YU, BINGTING; SILVA, RODRIGO A.; PHILLIPS, WAYNE A.; MAGIEROWSKI, MARCIN; VAN DE WINKEL, ANOUK; STADLER, H. SCOTT; et al. OXA13 in etiology and oncogenic potential of Barrett's esophagu. NATURE COMMUNICATIONS, v. 12, n. 1, JUN 7 2021. (16/01139-0, 17/01046-5)

DA SILVA, RODRIGO A.; FELTRAN, GEORGIA DA S.; FERNANDES, CELIO JUNIOR DA C.; ZAMBUZZI, WILLIAN F.. Osteogenic gene markers are epigenetically reprogrammed during contractile-to-calcifying vascular smooth muscle cell phenotype transition. CELLULAR SIGNALLING, v. 66, FEB 2020. (14/22689-3, 16/01139-0)

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. (16/01139-0, 14/22689-3, 16/08888-9)

BARROS, LEONARDO; EICHWALD, TUANY; SOLANO, ALEXANDRE FRANCISCO; SCHEFFER, DEBORA; DA SILVA, RODRIGO AUGUSTO; GASPAR, JOANA M.; LATINI, ALEXANDRA. Epigenetic modifications induced by exercise: Drug-free intervention to improve cognitive deficits associated with obesity. Physiology & Behavior, v. 204, p. 309-323, MAY 15 2019. (16/01139-0)

DA SILVA, RODRIGO A.; FERREIRA, MARCEL RODRIGUES; GOMES, ANDERSON MOREIRA; ZAMBUZZI, WILLIAN F.. LncRNA HOTAIR is a novel endothelial mechanosensitive gene. Journal of Cellular Physiology, v. 235, n. 5, p. 12-pg., 2019-10-21. (14/22689-3, 16/01139-0)

JANMAAT, VINCENT T.; LIU, HUI; DA SILVA, RODRIGO A.; WISSE, PIETER H. A.; SPAANDER, MANON C. W.; TEN HAGEN, TIMO L. M.; SMITS, RON; BRUNO, MARCO J.; FUHLER, GWENNY M.; PEPPELENBOSCH, MAIKEL P.. HOXA9 mediates and marks premalignant compartment size expansion in colonic adenomas. Carcinogenesis, v. 40, n. 12, p. 1514-1524, DEC 2019. (16/01139-0, 16/08888-9)

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.; et al. HOXA cluster gene expression during osteoblast differentiation involves epigenetic control. BONE, v. 125, p. 74-86, AUG 2019. (16/01139-0, 14/22689-3, 17/01046-5)

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. (16/10392-1, 16/01139-0, 14/22689-3)

JANMAAT, VINCENT T.; NESTERUK, KATERYNA; SPAANDER, MANON C. W.; VERHAAR, AUKE P.; YU, BINGTING; SILVA, RODRIGO A.; PHILLIPS, WAYNE A.; MAGIEROWSKI, MARCIN; VAN DE WINKEL, ANOUK; STADLER, H. SCOTT; et al. HOXA13 in etiology and oncogenic potential of Barrett's esophagus. NATURE COMMUNICATIONS, v. 12, n. 1, p. 17-pg., 2021-06-07. (17/01046-5, 16/01139-0)