Bone Abstracts

It is well known that thyroid hormone (TH) is essential for normal bone growth and development. 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. In vivo studies by our group have shown that TH interacts with the SNS to regulate bone mass and structure, and that this interaction involves α₂ adrenoceptor (α₂-AR) signaling. We also identified the presence of α_2A-, α_2B-, and α_2C-AR subtypes in the epiphyseal growth plate (EGP) of mice. In addition, we found that mice with isolated gene deletion of α_2A-AR and α_2C-AR (α_2A-AR^−/− and α_2C-AR^−/−) show a disorganized EGP, smaller long bones and a delay in endochondral ossification. Moreover, we found that the EGP of α_2A-AR^−/− and α_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 if α_2C-AR is involved in this process. We evaluated the linear bone growth of the femur and tibia derived from wild-type (WT) and α_2C-AR^−/− neonate mice for 12 days. We observed that 10⁻⁸ M triiodothyronine (T3) treatment for the whole culture period of twelve days significantly decreased bone linear growth of both femur and tibia only in WT animals. The linear growth of the bones derived from KO animals was not affect by T3 treatment. These in vitro findings suggest that TH locally interacts with the SNS to control bone linear growth and that this interaction involves α_2C-AR signaling.