Thyroid hormone interaction with the sympathetic nervous system, via ±2 adrenoceptor signaling, to regulate the endochondral bone growth: an in vitro evaluation

• Grant number: 16/01625-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 01, 2016
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Cecilia Helena de Azevedo Gouveia
• Grantee: Manuela Miranda Rodrigues
• Supervisor: Frank Beier
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Western University , Canada
• Associated to the scholarship: 14/19020-4 - Study of the interaction between thyroid hormone and the alpha2Adrenergic system in the endochondral bone growth: an organ culture evaluation (femur and tibia), BP.DR

Abstract

It is well known that thyroid hormone (TH) is essential for normal bone development and growth. However, the mechanisms by which TH regulates these processes are poorly understood. Recently, the sympathetic nervous system (SNS) was identified as a potent regulator of bone metabolism. We have shown that ±2 adrenoceptors (±2-AR) mediate the SNS actions in the skeleton, as well as the TH-SNS interactions to regulate bone mass and structure. We also identified the presence of ±2A-, ±2B-, and ±2C-AR isotypes in the epiphyseal growth plate (EGP) of mice.We found that mice with isolated gene deletion of ±2A-AR and ±2C-AR (±2A-AR-/- and ±2C-AR-/-) show a disorganized EGP, shorter long bones and a delay in endochondral ossification. Moreover, we found that the EGP of ±2A-AR-/- and ±2C-AR-/- animals respond differently, than those of wild-type animals, to TH excess and deficiency. These in vivo findings strongly suggest that TH also interacts with the SNS to regulate bone growth and development. Through a long bone organ culture system, the present study aims to investigate if TH interacts with the SNS directly in the skeleton, to regulate bone linear growth and development and if ±2-AR isotypes are involved in these processes. We believe that the findings of the present study will help to reveal unknown mechanisms by which TH interacts with the SNS to regulate skeletal development. (AU)