...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Aging cell. >Loss of glucocorticoid rhythm induces an osteoporotic phenotype in female mice
【24h】

Loss of glucocorticoid rhythm induces an osteoporotic phenotype in female mice

机译：糖皮质激素节律的丧失诱导女性小鼠骨质疏松表型

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Glucocorticoid (GC)-induced osteoporosis is a widespread health problem that is accompanied with increased fracture risk. Detrimental effects of anti-inflammatory GC therapy on bone have been ascribed to the excess in GC exposure, but it is unknown whether there is also a role for disruption of the endogenous GC rhythm that is inherent to GC therapy. To investigate this, we implanted female C57Bl/6J mice with slow-release corticosterone (CORT) pellets to blunt the rhythm in CORT levels without inducing hypercortisolism. Flattening of CORT rhythm reduced cortical and trabecular bone volume and thickness, whilst bone structure was maintained in mice injected with supraphysiologic CORT at the time of their endogenous GC peak. Mechanistically, mice with a flattened CORT rhythm showed disrupted circadian gene expression patterns in bone, along with changes in circulating bone turnover markers indicative of a negative balance in bone remodelling. Indeed, double calcein labelling of bone in vivo revealed a reduced bone formation in mice with a flattened CORT rhythm. Collectively, these perturbations in bone turnover and structure decreased bone strength and stiffness, as determined by mechanical testing. In conclusion, we demonstrate for the first time that flattening of the GC rhythm disrupts the circadian clock in bone and results in an osteoporotic phenotype in mice. Our findings indicate that at least part of the fracture risk associated with GC therapy may be the consequence of a disturbed GC rhythm, rather than excess GC exposure alone, and that a dampened GC rhythm may contribute to the age-related risk of osteoporosis.
机译：糖皮质激素（GC）诱导的骨质疏松症是一种广泛的健康问题，伴随着增加的骨折风险。抗炎GC疗法对骨骼的不利影响已归因于GC暴露中的过量，但是未知是否还存在用于中断GC疗法固有的内源性GC节律的作用。为了研究这一点，我们用缓释皮质酮（皮质）颗粒植入雌性C57BL / 6J小鼠，以在没有诱导高剖腹镜的情况下在皮质水溶液中剥离节奏。皮质节奏的平整化减少皮质和骨骨体积和厚度，而在其内源性GC峰时，将骨结构维持在注射超级病理学皮层的小鼠中。机械地，具有扁平皮质节奏的小鼠在骨中显示出中断的昼夜节律基因表达模式，以及指示骨重塑中负平衡的循环骨周转标记的变化。实际上，体内骨骼的双重穴异素标记显示小鼠的骨形成降低，扁平的皮质节奏。通过机械测试确定，集体，这些骨质周转和结构的扰动降低了骨强度和刚度。总之，我们首次证明了GC节奏的趋势损坏了核心时钟，并导致小鼠骨质疏松表型。我们的研究结果表明，与GC疗法相关的至少一部分骨折风险可能是扰动的GC节律的结果，而不是单独过量的GC暴露，并且抑制的GC节律可能有助于骨质疏松症的年龄相关风险。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号