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Local interaction of thyroid hormone with the alfa 2-adrenoceptor system on Endocondral bone development and growth: an evaluation in organ culture and chondrocyte primary culture

Grant number: 15/10671-5
Support Opportunities:Regular Research Grants
Duration: November 01, 2015 - October 31, 2017
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


It is known that thyroid hormone (TH) is essential for normal bone development. However, the mechanisms by which TH regulates this process are poorly understood. Recently, the sympathetic nervous system (SNS) was identified as a potent regulator of bone metabolism. Studies by our group have shown that ±2adrenoceptor (±2-AR) mediates the SNS actions in the skeleton, and that this system interacts with TH to regulate the bone mass and structure. We also identified the presence of adrenoceptors±2A, ±2B, and ±2C (±2A-AR, ±2B-AR and ±2C-AR) in the epiphyseal growth plate (EGP) of mice. In mice with isolated gene deletion of alfa 2A-AR and alfa 2C-AR (a2A-AR-/- and a2C-AR-/-), we observed that the EGP morphology is altered, the long bones are smaller compared to those of wild-type (WT) animals and that there is a delay in endochondral ossification. Moreover, we demonstrated that the effects of TH on the EGP morphology and on the longitudinal bone growth are also altered in a2A-AR-/- and a2C-AR-/-animals as compared with WT animals. These findings strongly suggest that TH also interacts with the SNS to regulate bone growth and development. On the other hand, it is not clear whether the SNS actions and its interaction with TH occur directly in the skeleton. Through a bone organ culture system of femurs and tibias and primary culture of chondrocytes derived from WT, a2A-AR-/- and a2C-AR-/- animals, this study aims to investigate (i) if a2A-AR and a2C-AR have direct action, i.e. local action (skeletal) on the bone growth and development of mice; and (ii) if TH interacts with a2A-AR and/or a2C-AR locally in the skeleton, to regulate these processes. The findings of this study may elucidate new mechanisms by which TH regulates the skeletal development. (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)
MARTINS, GISELA M.; TEIXEIRA, MARILIA B. C. G.; SILVA, V, MARCOS; NEOFITI-PAPI, BIANCA; MIRANDA-RODRIGUES, MANUELA; BRUM, PATRICIA C.; GOUVEIA, CECILIA H. A.. Global Disruption of alpha 2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone. FRONTIERS IN ENDOCRINOLOGY, v. 9, . (17/27023-1, 15/10671-5)

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