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

Grant number: 10/06409-0
Support Opportunities:Regular Research Grants
Duration: August 01, 2010 - July 31, 2013
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Cecilia Helena de Azevedo Gouveia
Grantee:Cecilia Helena de Azevedo Gouveia
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Patricia Chakur Brum


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 suggests 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 alfa2A and alfa2C (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 the 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 and A2C-AR interfere in bone structure and physiology, characterizing the bone phenotype of A2A-AR-/- and A2C-AR-/- mice and (ii) evaluate if the action of TH on bone tissue depends on A2A-AR and/or A2C-AR, analyzing the effect of TH on bone structure and physiology of A2A-AR-/- and A2C-AR-/- mice. We believe that this study might bring new information regarding the central regulation of bone structure and physiology; besides an important contribution to the understanding of the mechanisms through which TH regulates 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)
CRUZ GRECCO TEIXEIRA, MARILIA BIANCA; MARTINS, GISELE MIYAMURA; MIRANDA-RODRIGUES, MANUELA; DE ARAUJO, IASMIN FERREIRA; OLIVEIRA, RICARDO; BRUM, PATRICIA CHAKUR; AZEVEDO GOUVEIA, CECILIA HELENA. Lack of alpha(2C)-Adrenoceptor Results in Contrasting Phenotypes of Long Bones and Vertebra and Prevents the Thyrotoxicosis-Induced Osteopenia. PLoS One, v. 11, n. 1, . (10/06409-0)
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)

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