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Study of the interaction between thyroid hormone and the alpha2Adrenergic system in the endochondral bone growth: an organ culture evaluation (femur and tibia)

Grant number: 14/19020-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2014
Effective date (End): February 28, 2018
Field of knowledge:Biological Sciences - Biology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Cecilia Helena de Azevedo Gouveia
Grantee:Manuela Miranda Rodrigues
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):16/01625-2 - Thyroid hormone interaction with the sympathetic nervous system, via ±2 adrenoceptor signaling, to regulate the endochondral bone growth: an in vitro evaluation, BE.EP.DR

Abstract

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 ±2 adrenoceptor (±2-AR) mediates the SNSactions in the skeleton, as well as the TH-SNS interactions to regulate 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 isolatedgene deletion of ±2A-AR and ±2C-AR (±2A-AR-/- and ±2C-AR-/-), we observed that the EGP morphology isaltered, 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 of ±2A-AR-/- and ±2C-AR-/-animals are also changed. These findings strongly suggest that TH also interacts with the SNS to regulate bone growth and development. These findings, however, do not show whether the SNS actions and its interaction with TH occur directly in the skeleton. Through a bone organ culture system of femurs and tibias derived from WT, ±2A-AR-/- and ±2C-AR-/- animals, this study aims to investigate (I) if ±2A-AR and ±2C-AR have direct action, i.e. local action (skeletal) on the bone growth and development of mice; and (II) if TH interacts with ±2A-AR and/or ±2C-AR directly in the skeleton, to regulate these processes. The findings of this study may help to elucidate new mechanisms by which TH regulates skeletal development. (AU)