Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased osteoblastic function and osteopenia
Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased osteoblastic function and osteopenia
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DOI：
10.1210/en.2002-220129
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发表时间：
2002-10-01
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
Skeletal细胞合成IGF及其六种IGF结合蛋白（IGFBP）。据报道，IGFBP-5在体外刺激骨细胞生长，并在体内选择成骨细胞功能的参数，但其对骨形成的实际影响尚未确定。我们研究了在骨钙素启动子控制下，IGFBP-5对两种过表达IGFBP-5的转基因小鼠骨重建的直接影响。静态和动态组织形态计量学显示，IGFBP-5转基因小鼠继发于骨小梁数量和厚度减少以及骨矿物质沉积率一过性降低的骨小梁体积一过性降低。成骨细胞数量正常，表明成骨细胞功能受损。破骨细胞数量和骨吸收正常。IGFBP-5转基因动物在4周龄时的总骨密度、椎骨骨密度和股骨骨密度降低了14-27%，但在老年动物中没有降低。表达IGFBP-5转基因的基质细胞与野生型动物的细胞相比，碱性磷酸酶、骨钙素、核心结合因子1和I型胶原转录物的表达降低。总之，在骨微环境中过度表达IGFBP-5的转基因小鼠具有骨小梁体积的短暂减少、成骨细胞功能受损和骨质减少。
Skeletal cells synthesize IGFs and their six IGF binding proteins (IGFBP). IGFBP-5 was reported to stimulate bone cell growth in vitro and selected parameters of osteoblastic function in vivo, but its actual effects on bone formation are not established. We investigated the direct effects of IGFBP-5 on bone remodeling in two lines of transgenic mice overexpressing IGFBP-5 under the control of the osteocalcin promoter. Static and dynamic histomorphometry revealed that IGFBP-5 transgenic mice had a transient decrease in trabecular bone volume secondary to reduced trabecular number and thickness and a transient decrease in bone mineral apposition rate. Osteoblast number was normal, indicating impaired osteoblastic function. Osteoclast number and bone resorption were normal. Total, vertebral, and femoral bone mineral densities were reduced in IGFBP-5 transgenics by 14-27% at 4 wk of age, but not in older animals. Stromal cells expressing the IGFBP-5 transgene displayed decreased expression of alkaline phosphatase, osteocalcin, core binding factor 1, and type I collagen transcripts when compared with cells from wild-type animals. In conclusion, transgenic mice overexpressing IGFBP-5 in the bone microenvironment have a transient decrease in trabecular bone volume, impaired osteoblastic function, and osteopenia.