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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2014
• End date: February 28, 2018
• Field of knowledge: Biological Sciences - Biology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Cecilia Helena de Azevedo Gouveia
• Grantee: Manuela Miranda Rodrigues
• Host 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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Manuela Miranda. Thyroid Hormone interaction with the sympathetic nervous system, via &;#945;2 adrenoceptor signaling, to regulate endochondral bone growth: and in vitro evaluation. [Ph.D. Thesis (Morphofunctional Sciences)]. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo; 2017.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.