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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop for osteoblastogenesis in embryonic stem cell cultures
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Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop for osteoblastogenesis in embryonic stem cell cultures

机译：促甲状腺激素在胚胎干细胞培养物中诱导成骨细胞生成的Wnt依赖性前馈环

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摘要

We have shown that the anterior pituitary hormone, thyroid-stimulating hormone (TSH), can bypass the thyroid to exert a direct protective effect on the skeleton. Thus, we have suggested that a low TSH level may contribute to the bone loss of hyperthyroidism that has been attributed traditionally to high thyroid hormone levels. Earlier mouse genetic, cell-based, and clinical studies together have established that TSH inhibits osteoclastic bone resorption., However, the direct influence of TSH on the osteoblast has remained unclear. Here, we have used a model system developed from murine ES cells, induced to form mature mineralizing osteoblasts, and show that TSH stimulates osteoblast differentiation primarily through the activation of protein kinase Cδ and the up-regulation of the noncanonical Wnt components frizzled and Wnt5a. We predict that a TSH-induced, fast-forward short loop in bone marrow permits Wnt5a production, which, in addition to enhancing osteoblast differentiation, also stimulates osteopro-tegerin secretion to attenuate bone resorption by neighboring osteoclasts. We surmise that this loop should uncouple bone formation from bone resorption with a net increase in bone mass, which is what has been observed upon injecting TSH.
机译：我们已经表明，垂体前叶激素（促甲状腺激素）可以绕过甲状腺对骨骼产生直接的保护作用。因此，我们建议低TSH水平可能导致甲亢的骨质流失，而传统上这归因于高甲状腺激素水平。早期的小鼠遗传，细胞和临床研究共同证实，TSH抑制破骨细胞的骨吸收。但是，TSH对成骨细胞的直接影响仍不清楚。在这里，我们使用了从鼠ES细胞开发的模型系统，诱导形成成熟的矿化成骨细胞，并显示TSH主要通过蛋白激酶Cδ的激活和非规范性Wnt组分卷曲和Wnt5a的上调来刺激成骨细胞分化。我们预测，TSH诱导的骨髓中快进短环允许Wnt5a的产生，除了增强成骨细胞的分化外，它还刺激骨原tegerin分泌，从而减弱邻近破骨细胞的骨吸收。我们推测，该循环应该使骨形成与骨吸收脱开，而骨质净增加，这是在注射TSH后观察到的。

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    Ramkumarie Baliram; Rauf Latif; Joshua Berkowitz; Simon Frid; Graziana Colaianni; Li Sun; Mone Zaidi; Terry F. Davies;

  • 作者单位

    Thyroid Research Laboratory Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnThyroid Research Laboratory Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnThyroid Research Laboratory Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnThyroid Research Laboratory Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnMount Sinai Bone Program, Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnMount Sinai Bone Program, Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnMount Sinai Bone Program, Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

    rnThyroid Research Laboratory Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029 Mount Sinai Bone Program, Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, NY 10029;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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