title: Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice.
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 T3 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, α(2A)-AR, and α(2C)-AR (α(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 μCT) of the femur and vertebra and on the biomechanical properties (maximum load, ultimate load, and stiffness) of the femur. Surprisingly, α(2A/2C)-AR(-/-) mice were resistant to most of these T3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T3 in the bone of α(2A/2C)-AR(-/-) and WT mice, respectively. β1-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T3 treatment only in α(2A/2C)-AR(-/-) mice. As expected, T3 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 α2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Tatiana L
authors.initials: TL
authors.lastname: Fonseca
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Marilia B C G
authors.initials: MB
authors.lastname: Teixeira
authors.forename: Manuela
authors.initials: M
authors.lastname: Miranda-Rodrigues
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Manuela
authors.initials: M
authors.lastname: Rodrigues-Miranda
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Marcos V
authors.initials: MV
authors.lastname: Silva
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Gisele M
authors.initials: GM
authors.lastname: Martins
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Cristiane C
authors.initials: CC
authors.lastname: Costa
authors.affiliation: Department of Internal Medicine, Renal Division, Federal University of São Paulo School of Medicine, São Paulo, Brazil; and.
authors.forename: Danielle Y
authors.initials: DY
authors.lastname: Arita
authors.affiliation: Department of Internal Medicine, Renal Division, Federal University of São Paulo School of Medicine, São Paulo, Brazil; and.
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Perez
authors.affiliation: Department of Internal Medicine, Renal Division, Federal University of São Paulo School of Medicine, São Paulo, Brazil; and.
authors.forename: Dulce E
authors.initials: DE
authors.lastname: Casarini
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; cgouveia@usp.br.
authors.forename: Cecilia H A
authors.initials: CH
authors.lastname: Gouveia
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D002395:Catecholamines / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology*; D013963:Thyroid Hormones / Q000378:metabolism / Q000494:pharmacology*; D016474:Weight-Bearing
chemical_list: D002395:Catecholamines; D013963:Thyroid Hormones
keywords: bone; sympathetic nervous system; thyroid hormone; α-adrenoceptors; β-adrenoceptors