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Evaluation of the interaction of thyroid hormone with the sympathetic nervous system, via alpha-2 adrenergic receptors, in the regulation of bone growth and maturation

Grant number: 12/11858-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2012
Effective date (End): March 24, 2016
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Cecilia Helena de Azevedo Gouveia
Grantee:Marcos Vinicius da Silva
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


One of the most important findings of the last years was that the ósseo remodelamento is subject to the control of the central nervous system (SNC), with the likeable nervous system (SNS) acting as efetor peripheral. A series of studies suggests that SNS regulates the mass negative óssea, acting exclusively saw receiver ±2-adrenergic (±2-AIR), Express in osteoblastos. However, recent studies of our group had demonstrated that mice with double inativação of the genes of the receiving adrenergics ±2A and ±2C (±2a/±2c-AIR) present fenótipo of high óssea mass (I LOVE), although to present chronic likeable hiperatividade and unbroken ±2-AIR. Moreover, we demonstrate that these mice knockouts (KO = with gênica inativação) are resistant to the induced osteopenia for the tiroideano hormone excess (HT). We observe, still, that mice with isolated inativação of ±2a-AIR or ±2c-AIR are resistant to the reduction of the induced ósseo longitudinal growth for tirotoxicose. We saw, still, for imunohistoquímica, that both the receivers (±2a-AIR and ±2c-AIR) are express in the fabric ósseo, in condrócitos of the zone of reserve and the zone daily pay-hipertrófica of the epifisiais blades and in hipertróficos condrócitos of secondary centers of ossificação of mice. These findings suggest strong that (i) ²2-AIR is not the only involved adrenoceptor in the control of the ósseo metabolism and that (II) the SNS interacts with the HT to not only regulate the mass óssea, but also the ósseo longitudinal growth. Moreover, our findings raise the hypotheses of that (i) ±2a-AIR and/or ±2c-AIR also present an important paper in the mediation of the actions of the SNS in the skeleton and that (II) these receivers are involved in the interaction of the HT with the SNS to regulate the ósseos metabolism, growth and development. In this project, we have as objective: (i) to evaluate if the isolated inativação of ±2a-AIR intervenes with the ósseo longitudinal growth and the endocondral and intramembranosa ossificação of mice; (II) to characterize fenótipo of the epifisial blade of ±2a-AIR mice; (III) to investigate if the action of the HT in the ósseo growth depends on ±2a-AIR, evaluating the effect of the HT in the structure of the epifisial blade and in the ósseo longitudinal growth of the KOs mice; (IV) to evaluate if known ways of action of the HT in the epifisial blade (it saw of the GH/IGF-1 and it saw of the Wnt/²-catenina) they are affected by the isolated inativação of ±2a-AIR; (v) to investigate if the action of the HT in the endocondral and intramembranosa ossificação depends on ±2a-AIR. The considered studies will be able to bring new information regarding the mechanisms through which the HT regulates the growth and development of the skeleton. (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)
FONSECA, TATIANA L.; TEIXEIRA, MARILIA B. C. G.; RODRIGUES-MIRANDA, MANUELA; SILVA, MARCOS V.; MARTINS, GISELE M.; COSTA, CRISTIANE C.; ARITA, DANIELLE Y.; PEREZ, JULIANA D.; CASARINI, DULCE E.; BRUM, PATRICIA C.; GOUVEIA, CECILIA H. A. Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 307, n. 4, p. E408-E418, AUG 15 2014. Web of Science Citations: 7.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Marcos Vinicius da. Evaluation of the interaction of thyroid hormone with the sympathetic nervous system , via α2A adrenergic receptor, the regulation of maturation and bone growth.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.

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