Endothelial-induced osteogenic phenotype: lessons from human iPSCs technology and epigenetic control

• Grant number: 18/10443-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): July 01, 2018
• Effective date (End): November 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Rodrigo Augusto da Silva
• Supervisor: Martín Alejandro Montecino Leonard
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Research place: Universidad Andrés Bello, Santiago (UNAB), Chile
• Associated to the scholarship: 16/01139-0 - Epigenetic modulation triggered by paracrine factors from endothelial cells on osteoblast, BP.PD

Abstract

Numerous studies have demonstrated bone tissue as a reliable endocrine organ interconnected with others, undergoing a physiological homeostasis, by an effective crosstalk among a repertory of cells. Locally, we know that osteogenesis is essential for bone turnover, as well as the consolidation of the fracture through regenerative mechanisms; and that these processes usually decrease with advancing age, leading to bone loss and increased incidence of fractures in elderly people. Based on epidemiological statistics, bone defects have been achieved as a public health problem, once the life expectancy of the wide-world population increases significantly. So, the strategies to guide the rebuilding of the lost tissue is a major challenge for surgeons in the area, often requiring the application of extra-site tissue or an artificial biomaterial allowing the functional repair. Despite its medical, social and economic importance, little progress has been made in relation to bioassay methodologies capable of classifying new therapies, maybe because there is few information regarding the crosstalk between bone and endothelial cells recapitulating the molecular track involved with the osteoblast differentiation from mesenchymal stem cells, mainly considering the epigenetic mechanism governing this process. On this sense, we now know that bone development and regeneration are complex, orchestrated by paracrine mechanisms of endothelial cell events mediated by intercellular signaling, with osteogenesis closely coupled to angiogenesis.With decisive financial support from FAPESP (2014/22689-3), it was possible to consolidate a new group of research on bone biology at Department of Chemistry and Biochemistry, IBB, UNESP, Botucatu-SP, where very interesting results have been achieved and very recently a kickoff point was made in regarding the epigenetic modulation on osteoblast metabolism responding to trophic factors from endothelial cells (BEPE: 2017/01046-5), considering DNA methylation and of non-coding RNA involvement. However, in order to have a global epigenetic mechanism involved in this contextualization, an important field of epigenetic regulation has not yet been explored; we need to considerate the effect of paracrine factors on the regulation of the genetic expression promoted by the posttranscriptional modifications of the histones and we aimed to explore now with this proposal. In order to develop this program, we getting in touch with Prof. Martín Alejandro Montecino Leonard, who is expert on the epigenetic-based bone cell structures wide world. Important ingredient to considerate for the success of this partnership is the closeness between Brazil and Chile, providing the opportunity to speed the exchange of knowledge and students between the groups. (AU)