Thyroid Hormone Receptor β Mediates Thyroid Hormone Effects on Bone Remodeling and Bone Mass
Thyroid Hormone Receptor β Mediates Thyroid Hormone Effects on Bone Remodeling and Bone Mass
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DOI：
10.1002/jbmr.432
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发表时间：
2011-09-01
影响因子：
6.2
通讯作者：
Chassande, Olivier
中科院分区：
文献类型：
--
作者：
Monfoulet, Laurent-Emmanuel;Rabier, Benedicte;Chassande, Olivier
过量的甲状腺激素（TH）在成人引起骨质疏松症和增加骨折的风险。然而，TH影响骨转换的机制尚未阐明。特别是，甲状腺激素受体（TR）同型在TH介导成骨细胞介导的骨形成和破骨细胞介导的骨吸收中的作用尚未确定。在本研究中，我们对成年野生型、TR α或TR β缺陷小鼠进行了实验性甲状腺功能减退或甲状腺功能亢进，并分析了TH状态对小梁骨结构和重塑参数的影响。在野生型小鼠中，过量的TH减少了骨体积和矿化。高TH浓度与高骨吸收活性相关，通过破骨细胞表面增加和血清骨吸收标志物浓度升高来评估。经th处理的小鼠血清骨形成标志物也较高。TR α缺乏不能阻止TH对骨体积、骨矿化、骨形成或骨吸收的作用。相比之下，在野生型小鼠中观察到，TR β缺乏阻断了过量TH的所有早期效应。然而，长期暴露于低或高TH浓度的TR β缺陷小鼠会引起骨结构和重塑参数的轻微改变。总之，我们的数据表明，TR β受体介导促甲状腺激素浓度的短暂变化对骨重塑产生的急性影响，而TR α受体介导促甲状腺激素代谢的慢性改变的长期影响。这些数据揭示了TRs各自在TH控制骨代谢中的作用。(C) 2011年美国骨与矿物研究学会。
Excess thyroid hormone (TH) in adults causes osteoporosis and increases fracture risk. However, the mechanisms by which TH affects bone turnover are not elucidated. In particular, the roles of thyroid hormone receptor (TR) isotypes in the mediation of TH effects on osteoblast-mediated bone formation and osteoclast-mediated bone resorption are not established. In this study we have induced experimental hypothyroidism or hyperthyroidism in adult wild-type, TR alpha- or TR beta-deficient mice and analyzed the effects of TH status on the structure and remodeling parameters of trabecular bone. In wild-type mice, excess TH decreased bone volume and mineralization. High TH concentrations were associated with a high bone-resorption activity, assessed by increased osteoclast surfaces and elevated concentrations of serum bone-resorption markers. Serum markers of bone formation also were higher in TH-treated mice. TR alpha deficiency did not prevent TH action on bone volume, bone mineralization, bone formation, or bone resorption. In contrast, TR beta deficiency blocked all the early effects of excess TH observed in wild-type mice. However, prolonged exposure to low or high TH concentrations of TR beta-deficient mice induced mild modifications of bone structure and remodeling parameters. Together our data suggest that TR beta receptors mediate the acute effects produced by transient changes of TH concentrations on bone remodeling, whereas TR alpha receptors mediate long-term effects of chronic alterations of TH metabolism. These data shed new light on the respective roles of TRs in the control of bone metabolism by TH. (C) 2011 American Society for Bone and Mineral Research.