Skeletal overexpression of noggin results in osteopenia and reduced bone formation
Skeletal overexpression of noggin results in osteopenia and reduced bone formation
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DOI：
10.1210/en.2002-220918
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发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Canalis, E
中科院分区：
文献类型：
--
作者：
Devlin, RD;Du, Z;Canalis, E
骨骼细胞合成骨形态发生蛋白和骨形态发生蛋白拮抗剂。Noggin是一种糖蛋白，它选择性地与BMP结合并拮抗BMP的作用。Noggin在成骨细胞中的表达是由BMPs诱导的，Noggin在体外反对BMPs对成骨细胞分化和功能的影响。然而，它在体内的作用尚不清楚。在骨钙素启动子的控制下，我们研究了noggin在体内对过表达noggin转基因小鼠骨重建的直接影响。诺金转基因公司在出生的第一个月就遭受了长骨骨折。总的、椎骨和股骨的骨密度降低了23-29%。股骨的静态和动态组织形态计量学显示，noggin转基因小鼠的骨小梁体积、骨小梁数量和骨形成率都有所降低。成骨细胞表面和成骨细胞数/骨小梁面积未见明显减少，提示成骨细胞功能受损。破骨细胞表面和数量正常/减少，骨吸收无增加，组织呈编织状。椎体微计算机断层扫描证实骨小梁体积和骨小梁数量减少。总之，在骨微环境中过度表达noggin的转基因小鼠减少了骨小梁体积，损害了成骨功能，导致骨量减少和骨折。
Skeletal cells synthesize bone morphogenetic proteins (BMPs) and BMP antagonists. Noggin is a glycoprotein that binds BMPs selectively and antagonizes BMP actions. Noggin expression in osteoblasts is induced by BMPs and noggin opposes the effects of BMPs on osteoblastic differentiation and function in vitro. However, its effects in vivo are not known. We investigated the direct in vivo effects of noggin on bone remodeling in transgenic mice overexpressing noggin under the control of the osteocalcin promoter. Noggin transgenics suffered long bone fractures in the first month of life. Total, vertebral, and femoral bone mineral densities were reduced by 23-29%. Static and dynamic histomorphometry of the femur revealed that noggin transgenic mice had decreased trabecular bone volume, number of trabeculae, and bone formation rate. Osteoblast surface and number of osteoblasts/trabecular area were not significantly decreased, indicating impaired osteoblastic function. Osteoclast surface and number were normal/decreased, there was no increase in bone resorption, and the tissue had the appearance of woven bone. Vertebral microcomputed tomography scanning confirmed decreased trabecular bone volume and trabecular number. In conclusion, transgenic mice overexpressing noggin in the bone microenvironment have decreased trabecular bone volume and impaired osteoblastic function, leading to osteopenia and fractures.