The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation.
The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation.
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DOI：
10.1084/jem.20041097
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发表时间：
2005-03-21
期刊：
影响因子：
--
通讯作者：
Noda M
中科院分区：
文献类型：
--
作者：
Morinobu M;Nakamoto T;Hino K;Tsuji K;Shen ZJ;Nakashima K;Nifuji A;Yamamoto H;Hirai H;Noda M
骨质疏松症是一个主要的健康问题，然而，调节成人骨量的机制知之甚少。Cas相互作用锌指蛋白（CIZ）是一种核质穿梭蛋白，定位于成骨细胞附着于基质的细胞粘附斑。为了研究CIZ在调节成人骨量中的潜在作用，我们检查了CIZ缺陷小鼠的骨骼。骨体积增加，骨形成率增加CIZ缺陷小鼠，而骨吸收没有改变。CIZ缺乏增强了编码成骨细胞表型相关蛋白质的基因的mRNA表达水平，如碱性磷酸酶（ALP）以及整个长骨中osterix mRNA的表达。从CIZ缺陷小鼠股骨获得的骨髓细胞在培养中显示出更高的ALP活性，并形成比野生型细胞更多的矿化结节。CIZ缺乏增强骨形态发生蛋白（BMP）诱导的骨髓细胞成骨细胞分化的文化，表明BMP是CIZ的行动的目标。CIZ缺乏增加体内股骨骨髓消融后新形成的骨量。最后，BMP-2诱导的骨形成在体内的成年小鼠颅骨上被CIZ缺乏所增强。这些结果证实CIZ通过抑制BMP诱导的成骨细胞活化来抑制成人骨量水平。
Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)–induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2–induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.
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DOI：
10.1084/jem.193.3.399
发表时间：
2001-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ishijima M;Rittling SR;Yamashita T;Tsuji K;Kurosawa H;Nifuji A;Denhardt DT;Noda M
通讯作者：
Noda M
影响因子：
3.7
作者：
Furuya, K;Nakamoto, T;Noda, M
通讯作者：
Noda, M
影响因子：
2.1
作者：
Nakamoto, T;Shiratsuchi, A;Hirai, H
通讯作者：
Hirai, H
影响因子：
4.1
作者：
Shimizu, T;Mehdi, R;Takaoka, K
通讯作者：
Takaoka, K
影响因子：
64.8
作者：
SASAI, Y;LU, B;DEROBERTIS, EM
通讯作者：
DEROBERTIS, EM