Objective

In humans, loss-of-function mutations in the gene encoding pregnancy-associated pregnancy protein-A2 cause short stature and slightly reduced bone density. The goal of this study was to determine the effects of Pappa2 deletion on bone in mice.

Design

Pappa2 deletion mice and littermate controls were culled at 10, 19 or 30 weeks of age and femurs were analysed by micro-computed tomography. Serum markers of bone turnover and insulin-like growth factor binding protein 5 (IGFBP-5), a proteolytic target of PAPP-A2, were measured by ELISA.

Results

At 10 and 19 weeks of age, Pappa2 deletion mice had slightly reduced trabecular parameters, but by 19 weeks of age, female deletion mice had increased cortical tissue mineral density, and this trait was increased by a small amount in deletion mice of both sexes at 30 weeks. Cortical area fraction was increased in Pappa2 deletion mice at all ages. Deletion of Pappa2 increased circulating IGFBP-5 levels and reduced markers of bone turnover (PINP and TRACP 5b).

Conclusions

PAPP-A2 contributes to the regulation of bone structure and mass in mice, likely through control of IGFBP-5 levels. The net effect of changes in bone formation and resorption depend on sex and age, and differ between trabecular and cortical bone.

中文翻译：

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Pappa2缺失对小鼠骨骼具有性别和年龄特异性。

目的

在人类中，与妊娠相关的妊娠蛋白-A2编码的基因中的功能丧失突变导致身材矮小和骨密度略有降低。这项研究的目的是确定Pappa2缺失对小鼠骨骼的影响。

设计

在10、19或30周龄时剔除Pappa2缺失小鼠和同窝对照，并通过显微计算机断层扫描对股骨进行分析。通过ELISA测量了骨转换的血清标志物和PAPP-A2的蛋白水解靶标胰岛素样生长因子结合蛋白5（IGFBP-5）。

结果

在10和19周龄时，Pappa2缺失小鼠的骨小梁参数略有降低，但是到19周龄时，雌性缺失小鼠的皮质组织矿物质密度增加，并且在两种性别的缺失小鼠中，这种特性都有少量增加。 30周。在所有年龄段的Pappa2缺失小鼠中，皮质面积分数均增加。删除Pappa2可增加循环IGFBP-5水平并减少骨转换标记（PINP和TRACP 5b）。

结论

PAPP-A2可能通过控制IGFBP-5水平来调节小鼠的骨结构和质量。骨形成和吸收变化的最终结果取决于性别和年龄，并且小梁和皮质骨之间存在差异。