Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis - A longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice
Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis - A longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice
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DOI：
10.1002/art.23454
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发表时间：
2008-06-01
影响因子：
--
通讯作者：
Lane, Nancy E.
中科院分区：
文献类型：
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作者：
Yao, Wei;Cheng, Zhiqiang;Lane, Nancy E.
Objective.糖皮质激素（GC）过量会引起骨代谢的改变，从而削弱骨结构并增加骨折风险。本研究的目的是通过微阵列分析鉴定GC处理小鼠骨代谢相关基因。在治疗0、7、28和56天后收集暴露于GC过量的小鼠的长骨，以测量骨微结构并提取RNA用于微阵列分析。通过微焦点计算机断层扫描测量的骨转换标志物和骨结构的变化证实了该动物模型中的骨丢失。GC过量诱导破骨细胞活化、功能和脂肪形成相关基因的早期上调，在第7天达到峰值。与破骨细胞细胞骨架重组相关的基因和与基质降解相关的基因的表达在第28天达到峰值。在第28天和第56天，与成骨细胞活化和成熟相关的基因的表达从基线降低，而Wnt拮抗剂的表达增加。此外，与骨矿化相关的骨细胞中表达的基因的表达在较晚的时间点，即第28天和第56天显著更高。逆转录-聚合酶链反应证实了微阵列分析的结果。GC过量与破骨细胞生成和脂肪生成相关基因的早期激活以及与骨生成和矿化相关基因的后期抑制相关。用调节Wnt信号传导或矿化的药物进行新的干预可能对GC诱导的骨质疏松症有效。
Objective. Glucocorticoid (GC) excess induces alterations in bone metabolism that weaken bone structure and increase fracture risk. The aim of this study was to identify genes associated with bone metabolism in GC-treated mice, by performing a microarray analysis.Methods. Long bones from mice exposed to GC excess were collected after 0, 7, 28, and 56 days of treatment, to measure bone microarchitecture and extract RNA for microarray analyses.Results. Bone loss in this animal model was confirmed by changes in bone turnover markers as well as bone architecture, as measured by microfocal computed tomography. GC excess induced an early up-regulation of genes involved in osteoclast activation, function, and adipogenesis, which peaked on day 7. The expression of genes associated with osteoclast cytoskeletal reorganization and genes associated with matrix degradation peaked on day 28. On day 28 and day 56, the expression of genes associated with osteoblast activation and maturation was decreased from baseline, while the expression of Wnt antagonists was increased. In addition, the expression of genes expressed in osteocytes associated with bone mineralization was significantly higher at the later time points, day 28 and day 56. Reverse transcription-polymerase chain reaction confirmed the results of microarray analysis in selected genes.Conclusion. GC excess is associated with early activation of genes associated with osteoclastogenesis and adipogenesis and a later suppression of genes associated with osteogenesis and mineralization. Novel interventions with agents that modulate either Wnt signaling or mineralization may be effective in GC- induced osteoporosis.