Lack of Schnurri-2 Expression Associates with Reduced Bone Remodeling and Osteopenia*
Lack of Schnurri-2 Expression Associates with Reduced Bone Remodeling and Osteopenia*
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DOI：
10.1074/jbc.m611203200
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发表时间：
2007-04
影响因子：
4.8
通讯作者：
Y. Saita;T. Takagi;Keiichiro Kitahara;M. Usui;K. Miyazono;Y. Ezura;K. Nakashima;H. Kurosawa;S. Ishii;M. Noda
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文献类型：
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作者：
Y. Saita;T. Takagi;Keiichiro Kitahara;M. Usui;K. Miyazono;Y. Ezura;K. Nakashima;H. Kurosawa;S. Ishii;M. Noda
骨重塑的调节决定了骨量的水平，骨量的不平衡会导致骨质疏松等主要骨骼疾病。锌指蛋白 Schnurri-2 (SHN-2) 最近被证明可以调节骨形态发生蛋白依赖性脂肪生成和淋巴生成。然而，SHN-2 在骨中的作用尚不清楚。在这里，我们研究了 Shn-2 缺陷对 Shn-2 缺失小鼠骨代谢和细胞功能的影响。 SHN-2表达的缺乏通过抑制体内成骨细胞骨形成和破骨细胞骨吸收活性来减少骨重塑。 Shn-2 缺陷会抑制 osterix 和骨钙蛋白的表达以及体外矿化。相反，Shn-2 过表达增强了骨钙素启动子活性和骨形态发生蛋白依赖性成骨细胞分化。 Shn-2 缺陷抑制 Nfatc1 和 c-fos 表达，导致体内和骨髓细胞培养中耐酒石酸酸性磷酸酶阳性细胞发育减少。这些研究表明 SHN-2 调节正常骨重塑所需的关键转录因子的活性。
Regulation of bone remodeling determines the levels of bone mass and its imbalance causes major skeletal diseases such as osteoporosis. A zinc finger protein, Schnurri-2 (SHN-2), was recently demonstrated to regulate bone morphogenetic protein-dependent adipogenesis and lymphogenesis. However, the role of SHN-2 in bone is not known. Here, we investigated the effects of Shn-2 deficiency on bone metabolism and cell function in Shn-2-null mice. Lack of SHN-2 expression reduced bone remodeling by suppressing both osteoblastic bone formation and osteoclastic bone resorption activities in vivo. Shn-2 deficiency suppressed osterix and osteocalcin expression as well as in vitro mineralization. Conversely, Shn-2 overexpression enhanced osteocalcin promoter activity and bone morphogenetic protein-dependent osteoblastic differentiation. Shn-2 deficiency suppressed Nfatc1 and c-fos expression leading to reduction of tartrate-resistant acid phosphatase-positive cell development in vivo as well as in the cultures of bone marrow cells. These studies demonstrate that SHN-2 regulates the activities of critical transcription factors required for normal bone remodeling.