Transforming Growth Factor Beta is regulated by a Glucocorticoid-Dependent Mechanism in Denervation Mouse Bone.

Transforming Growth Factor Beta is regulated by a Glucocorticoid-Dependent Mechanism in Denervation Mouse Bone.
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转化生长因子 Beta 受去神经小鼠骨中糖皮质激素依赖性机制的调节。

DOI:
10.1038/s41598-017-09793-y
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发表时间:
2017-08-30
期刊:
影响因子:
4.6
通讯作者:
Du H
Du H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Y;Jie L;Tian AY;Zhong S;Tian MY;Zhong Y;Wang Y;Li H;Li J;Sun X;Du H

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在成人和儿童中,去神经支配抑制骨生长和重塑,导致线性生长和骨量的改变,并增加骨质疏松症和病理性骨折的风险。转化生长因子β(TGF-β)同种型是促进骨形成的一组关键生长因子。为了探讨去神经诱导的骨形成减少与TGF-β基因表达的关系,我们检测了去神经小鼠骨中TGF-β的mRNA水平,发现TGF-β1、TGF-β2和TGF-β3的mRNA水平降低。这些变化伴随着体重减轻、骨矿物质密度(BMD)、骨小梁厚度、股骨和腰椎骨小梁分离和骨小梁数量、血清骨钙素、总钙、全段甲状旁腺激素和血清C端肽升高。重组人TGF-β1(rhTGF-β1)可预防去神经诱导的骨密度降低,进一步支持了我们的假设,即去神经诱导的骨形成减少是TGF-β基因表达抑制的结果。此外,抗孕激素RU 38486可减弱去神经诱导的TGF-β组mRNA水平的降低,而地塞米松(DEX)则可降低正常小鼠TGF-β组mRNA水平。此外,失神经小鼠的血浆皮质酮增加了三倍。这些结果表明,去神经诱导的骨形成减少可能是由糖皮质激素通过抑制TGF-β基因表达至少部分调节。
Bone growth and remodeling is inhibited by denervation in adults and children, resulting in alterations of linear growth and bone mass and increased risk for osteoporosis and pathologic fractures. Transforming growth factor beta (TGF-β) isoforms are a key group of growth factors that enhance bone formation. To explore the relation between denervation-induced reduction of bone formation and TGF-β gene expression, we measured mRNA levels of TGF-β in denervation mouse bone and found decreased mRNA levels of TGF-β1, TGF-β2 and TGF-β3. These changes were accompanied by diminishing weight loss, bone mineral density (BMD), trabecular thickness, trabecular separation and trabecular number of femur and lumbar, serum osteocalcin, total calcium, intact parathyroid hormone, and increased serum C telopeptide. Recombinant human TGF-β1 (rhTGF-β1) prevented denervation-induced reduction of BMD further supporting our hypothesis that denervation-induced reduction of bone formation is a result of inhibition of TGF-β gene expression. In addition, antiprogestins RU 38486 blunted the denervation-induced decrease in mRNA levels of TGF-β group, while dexamethasone (DEX) decreased TGF-β group mRNA levels in normal mice. Furthermore, the denervated-mice exhibited a threefold increase in plasma corticosterone. These results suggest that denervation-induced reduction of bone formation may be regulated by glucocorticoids via inhibition of TGF-β gene expression at least in part.
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