NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation.

NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation.
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DOI:
10.1016/j.febslet.2011.06.024
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发表时间:
2011-08-04
期刊:
影响因子:
3.5
通讯作者:
Zhang X
Zhang X
中科院分区:
生物学3区
文献类型:
--
作者:
Zou X;Shen J;Chen F;Ting K;Zheng Z;Pang S;Zara JN;Adams JS;Soo C;Zhang X

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NELL-1是一种与颅骨缝过早闭合相关的骨诱导分子。在这里,我们确定APR 3,膜蛋白被称为增殖抑制因子,作为一个结合蛋白的NELL-1的生物淘选。NELL-1和APR 3共定位于人成骨细胞的核被膜上。NELL-1通过进一步下调Cyclin D1的表达而显著抑制与APR 3共转染的成骨细胞的增殖。NELL-1和APR 3的共表达增强了Ocn和Bsp的表达和矿化。APR 3的RNAi显著降低了NELL-1的分化效果。这些结果表明,NELL-1对成骨细胞分化和增殖的影响部分是通过与APR 3结合。
NELL-1 is an osteoinductive molecule associated with premature calvarial suture closure. Here we identified APR3, a membrane protein known as a proliferation suppressor, as a binding protein of NELL-1 by biopanning. NELL-1 and APR3 colocalized on the nuclear envelope of human osteoblasts. NELL-1 significantly inhibited proliferation of osteoblasts co-transfected with APR3 through further down-regulation of Cyclin D1. The co-expression of NELL-1 and APR3 enhanced Ocn and Bsp expression and mineralization. RNAi of APR3 significantly reduced the differentiation effect of NELL-1. These findings suggest that the effects of NELL-1 on osteoblastic differentiation and proliferation are partly through binding to APR3.
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