Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
Department of Endocrinology, the Second Hospital of Shandong University, Jinan, Shandong Province 250033, China.
J Biomech. 2014 Apr 11;47(6):1307-14. doi: 10.1016/j.jbiomech.2014.02.015. Epub 2014 Feb 19.
It has been suggested that pituitary hormone might be associated with bone metabolism. To investigate the role of thyroid-stimulating hormone (TSH) in bone metabolism, we designed the present study as follows. After weaning, TSH receptor (TSHR) null mice (Tshr(-/-)) were randomly divided into a thyroxine treatment group (n=10) or non-treatment group (n=10); the treatment group received a dose of desiccated thyroid extract at 100 ppm daily for 5 weeks. Age-matched wild-type (Tshr(+/+), n=10) and heterozygote mice (Tshr(+/-), n=10) served as controls. After 5 weeks, the animals were sacrificed, and the femurs were collected for histomorphometrical and biomechanical analyses. In addition, the effect of TSH on osteoclastogenesis was examined in the RAW264.7 osteoclast cell line. We found that compared with Tshr(+/+) mice, Tshr(-/-) and Tshr(+/-) mice had lower bone strength. The histomorphometric results showed that trabecular bone volume, osteoid surface, osteoid thickness and osteoblast surface were significantly decreased, whereas the osteoclast surface was significantly increased in both Tshr(-/-) and Tshr(+/-) mice compared with Tshr(+/+) mice. Bone resorption and formation in Tshr(-/-) mice were further enhanced by thyroxine replacement. bTSH inhibited osteoclast differentiation in vitro, as demonstrated by reduced development of TRAP-positive cells and down-regulation of differentiation markers, including tartrate-resistant acid phosphatase, matrix metallo-proteinase-9 and cathepsin K in RAW264.7 cells. Our results confirm that TSH increased bone volume and improved bone microarchitecture and strength at least partly by inhibiting osteoclastogenesis.
有人提出，垂体激素可能与骨代谢有关。为了研究促甲状腺激素（TSH）在骨代谢中的作用，我们设计了如下研究。断奶后，TSH 受体（TSHR）缺失小鼠（Tshr(-/-)）被随机分为甲状腺素治疗组（n=10）或非治疗组（n=10）；治疗组每天接受 100ppm 的干甲状腺提取物治疗 5 周。年龄匹配的野生型（Tshr(+/+)，n=10）和杂合子小鼠（Tshr(+/-)，n=10）作为对照。5 周后，处死动物，收集股骨进行组织形态计量学和生物力学分析。此外，还在 RAW264.7 破骨细胞系中检测了 TSH 对破骨细胞生成的影响。我们发现，与 Tshr(+/+)小鼠相比，Tshr(-/-)和 Tshr(+/-)小鼠的骨强度较低。组织形态计量学结果显示，小梁骨体积、骨样表面、骨样厚度和成骨细胞表面均显著降低，而 Tshr(-/-)和 Tshr(+/-)小鼠的破骨细胞表面均显著高于 Tshr(+/+)小鼠。用甲状腺素替代治疗进一步增强了 Tshr(-/-)小鼠的骨吸收和形成。bTSH 在体外抑制破骨细胞分化，表现为 TRAP 阳性细胞的发育减少和分化标志物，包括抗酒石酸酸性磷酸酶、基质金属蛋白酶-9 和组织蛋白酶 K 的下调。我们的研究结果证实，TSH 通过抑制破骨细胞生成，至少部分增加了骨量，改善了骨微结构和强度。
