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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes
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Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes

机译：骨细胞中的雄激素受体（AR）对于维持男性骨骼完整性很重要：小鼠骨细胞中靶向性AR破坏的证据

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摘要

Androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling has been mainly attributed to osteoblasts. Although osteocytes have emerged as key regulators of bone remodeling, the influence of sex steroids on these cells has been poorly studied. We aimed to investigate the role of AR signaling, specifically in osteocytes using the Cre/LoxP system in male mice (driven by dentin matrix protein 1 [ocy-ARKOs]). Osteocyte fractions of control (AR(ex2)/Y) and ocy-ARKO (ARflox(ex2)/Y; DMP1-cre) mice isolated through sequential collagenase digestion showed increasing AR expression toward the mature osteocyte fraction of control males compared with the more immature fractions, whereas this was reduced by 80% in ocy-ARKO osteocytes. The skeletal phenotype of mutant mice was further assessed by histomorphometry and quantitative micro-computed tomography at 12 and 32 weeks of age. Ocy-ARKOs had significantly lower trabecular bone volume and number in femora and tibias at 32 weeks as well as decreased trabecular number in the L5 vertebra at 12 weeks. Biomechanical testing showed that ocy-ARKO femora were also stiffer and required a lower ultimate force to induce failure at 32 weeks. However, femoral cortical structure was not significantly different at any time point. The absence of AR in osteocyte also did not appear to affect trabecular bone formation nor its response to mechanical loading. In conclusion, selective inactivation of the AR in osteocytes of male mice accelerates age-related deterioration of skeletal integrity. These findings provide evidence for a direct role of androgens in the maintenance of trabecular bone through actions of the AR in osteocytes.
机译：雄激素在维持男性骨骼完整性中起关键作用。雄激素受体（AR）信号传导对这种完整性的调节主要归因于成骨细胞。尽管骨细胞已成为骨重塑的关键调节因子，但对性类固醇对这些细胞的影响研究却很少。我们旨在研究AR信号的作用，特别是在雄性小鼠中使用Cre / LoxP系统（由牙本质基质蛋白1 [ocy-ARKOs驱动]）在AR细胞中的作用。通过顺序胶原酶消化分离的对照（AR（ex2）/ Y）和ocy-ARKO（ARflox（ex2 / Y; DMP1-cre））小鼠的骨细胞分数显示，与对照雄性成年骨细胞分数相比，AR表达增加未成熟部分，而在ocy-ARKO骨细胞中减少了80％以上。通过组织形态计量学和定量微计算机断层扫描在12和32周龄时进一步评估突变小鼠的骨骼表型。 Ocy-ARKOs在第32周时的股骨和胫骨中的小梁骨数量和数量显着降低，而在第5周时L5椎骨中的小梁数量减少。生物力学测试表明，ocy-ARKO股骨也较硬，需要较低的极限力才能在32周时诱发衰竭。但是，股骨皮质结构在任何时间点都没有显着差异。骨细胞中不存在AR似乎也不会影响小梁的骨形成及其对机械负荷的反应。总之，雄性小鼠骨细胞中AR的选择性失活会加速与年龄相关的骨骼完整性恶化。这些发现为雄激素通过AR在骨细胞中的作用在小梁骨维持中的直接作用提供了证据。

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