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Evaluation of the effect of thyroid hormone on bone structure and physiology of mice with gene inactivation of the alpha 2A adrenoceptor

Grant number: 10/04911-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2010
Effective date (End): July 31, 2012
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Cecilia Helena de Azevedo Gouveia
Grantee:Gisele Miyamura Martins
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


One of the most important findings of the recent years is that bone remodeling is under control of the central nervous system (SNC), with the sympathetic nervous system (SNS) acting as the peripheral effector. A series of studies suggest that the SNS negatively regulates bone mass, acting exclusively via beta2-adrenoceptor (B2-AR), which is expressed in osteoblasts. However, a recent study of our group demonstrated that mice with double gene inactivation of the adrenoceptor alpha2A and alpha2C (A2A/A2C-AR-/-) present a phenotype of high bone mass (HBM), in spite of presenting chronic sympathetic hyperactivity and intact B2-AR. Furthermore, we demonstrated that these knockout (KO) mice are resistant to the thyroid hormone (TH)-induced osteopenia. In addition, we found that, in bone of wild type (WT) mice, both receptors (A2A-AR and A2C-AR) are expressed, that A2A-AR is more expressed than A2C-AR, and that gene expression of A2C-AR is regulated by TH. These findings strongly suggest that (i) B2-AR is not the sole adrenoceptor involved in the control of bone metabolism and that (ii) the SNS interacts with TH to regulate bone mass. Besides, our findings raise the hypothesis that (i) A2A-AR and/or A2C-AR also present an important role in mediating the actions of the SNS in the skeleton and that (ii) these receptors are involved in the TH-SNS interaction to regulate bone mass and bone metabolism. In the present project, we aim to (i) evaluate if the isolated inactivation of A2A-AR interfere in bone structure and physiology, characterizing the bone phenotype of A2A-AR KO mice. We believe that this study might contribute to the understanding of the mechanisms through which the SNS and TH regulate bone mass and structure, which may contribute to the treatment of bone diseases, including osteoporosis. (AU)

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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.; et al. 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, . (10/04911-0, 13/02247-3, 12/11858-3, 10/06409-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MARTINS, Gisele Miyamura. Evaluation of the effect of thyroid hormone on bone structure and physiology of mice with inactivation of Gene a2A-adrenoceptor.. 2013. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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