| First Author | Fonseca TL | Year | 2014 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 307 |
| Issue | 4 | Pages | E408-18 |
| PubMed ID | 25005498 | Mgi Jnum | J:215639 |
| Mgi Id | MGI:5605937 | Doi | 10.1152/ajpendo.00643.2013 |
| Citation | Fonseca TL, et al. (2014) Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice. Am J Physiol Endocrinol Metab 307(4):E408-18 |
| abstractText | 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, 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 muCT) 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 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 alpha(2A/2C)-AR(-/-) and WT mice, respectively. beta1-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T3 treatment only in alpha(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 alpha2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology. |
