LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development
LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development
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DOI：
10.1016/s0092-8674(01)00571-2
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发表时间：
2001-11-16
期刊：
影响因子：
64.5
通讯作者：
Warman, ML
中科院分区：
文献类型：
--
作者：
Gong, YQ;Slee, RB;Warman, ML
在人类中，低峰值骨量是骨质疏松症的重要危险因素。我们报告LRP 5，编码低密度脂蛋白受体相关蛋白5，影响生长过程中的骨量增加。LRP 5的突变导致常染色体隐性遗传疾病神经胶质瘤-假神经胶质瘤综合征（OPPG）。我们发现OPPG携带者与年龄和性别匹配的对照组相比骨量减少。我们证明了LRP 5在成骨细胞中的原位表达，并表明LRP 5可以通过经典途径在体外抑制Writ信号传导。我们进一步表明，在小鼠颅骨外植体培养中，LRP 5的一种分泌形式可以减少骨厚度。这些数据表明，Wnt介导的信号传导通过LRP 5影响生长期间的骨积累，并且对于峰值骨量的建立是重要的。
In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Writ signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.