Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice

Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice

Author Fonseca, Tatiana L. Google Scholar
Teixeira, Marilia B. C. G. Google Scholar
Rodrigues-Miranda, Manuela Google Scholar
Silva, Marcos V. Google Scholar
Martins, Gisele M. Google Scholar
Costa, Cristiane C. Google Scholar
Arita, Danielle Y. Autor UNIFESP Google Scholar
Perez, Juliana D. Autor UNIFESP Google Scholar
Casarini, Dulce E. Autor UNIFESP Google Scholar
Brum, Patricia C. Google Scholar
Gouveia, Cecilia H. A. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract To investigate whether thyroid hormone (TH) interacts with the sympathetic nervous system (SNS) to modulate bone mass and structure, we studied the effects of daily T-3 treatment in a supraphysiological dose for 12 wk on the bone of young adult mice with chronic sympathetic hyperactivity owing to double-gene disruption of adrenoceptors that negatively regulate norepinephrine release, alpha(2A)-AR, and alpha(2C)-AR (alpha(2A/2C)-AR(-/-) mice). As expected, T3 treatment caused a generalized decrease in the areal bone mineral density (aBMD) of WT mice (determined by DEXA), followed by deleterious effects on the trabecular and cortical bone microstructural parameters (determined by mu CT) of the femur and vertebra and on the biomechanical properties (maximum load, ultimate load, and stiffness) of the femur. Surprisingly, alpha(2A/2C)-AR(-/-) mice were resistant to most of these T-3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T-3 in the bone of alpha(2A/2C)-AR(-/-) and WT mice, respectively. beta(1)-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T-3 treatment only in alpha(2A/2C)-AR(-/-) mice. As expected, T-3 inhibited the cell growth of calvaria-derived osteoblasts isolated from WT mice, but this effect was abolished or reverted in cells isolated from KO mice. Collectively, these findings support the hypothesis of a TH-SNS interaction to control bone mass and structure of young adult mice and suggests that this interaction may involve alpha(2)-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology.
Keywords thyroid hormone
sympathetic nervous system
bone
alpha-adrenoceptors
beta-adrenoceptors
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2010/06409-0
FAPESP: 2013/02247-3
FAPESP: 05/59557-8
FAPESP: 10/50068-2
FAPESP: 2012/11858-3
FAPESP: 10/04911-0
FAPESP: 09/52485-2
Date 2014-08-15
Published in American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 307, n. 4, p. E408-E418, 2014.
ISSN 0193-1849 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent E408-E418
Origin http://dx.doi.org/10.1152/ajpendo.00643.2013
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000341709700006
URI http://repositorio.unifesp.br/handle/11600/38093

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