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首页> 外文期刊>Endocrine Connections >Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans
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Regulation of sclerostin in glucocorticoid-induced osteoporosis (GIO) in mice and humans

机译：硬化素在糖皮质激素诱发的小鼠和人类骨质疏松症（GIO）中的调节

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Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n ?=?101) and polymyalgia rheumatica (PMR, n ?=?21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and sex-matched controls (?40%, P ?&?0.01 and ?26.5%, P ?&?0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.
机译：糖皮质激素（GC）用于治疗炎症疾病，包括各种形式的关节炎。但是，它们的使用尤其受到对骨骼的不利影响的限制。 Wnt和骨形成抑制剂硬化蛋白最近与GC诱导的骨质疏松症的发病机理有关。但是，数据是模棱两可的。这项研究的目的是使用几种高GC水平的小鼠模型和两个独立的接受GC治疗的患者队列，评估GC对硬化素的调节作用。暴露于GC的雄性24周龄C57BL / 6和18周龄DBA / 1小鼠和内源性皮质醇过多的12周龄小鼠显示出骨形成减少，P1NP水平降低和血清硬化素水平升高表明。然而，硬化素在股骨组织和经GC处理的骨髓基质细胞中的表达并没有持续改变。相比之下，GC在人间质基质细胞的mRNA和蛋白质水平上均抑制了硬化素的mRNA和蛋白质水平，并且这种作用是GC受体依赖性的。与人类细胞培养数据一致，暴露于GC的类风湿性关节炎（RA，n≥102）和风湿性多肌痛（PMR，n≥21）患者的硬化素血清水平低于健康的年龄段和年龄段。性别匹配的对照组（分别为40％，P <0.01，和26.5％，P <0.001）。总而言之，硬化蛋白似乎在小鼠和人类中受到GC的差异调节，因为它在人类中受到GC的抑制，但在小鼠中并未持续改变。需要进一步的研究来描述小鼠和人类中硬化蛋白的GC调节之间的差异，并评估硬化素是否介导GC诱导的人类骨质疏松症。

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