Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation.
Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation.
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DOI：
10.1210/endo.141.7.7585
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发表时间：
2000-07
期刊：
影响因子：
4.8
通讯作者：
Guisheng Zhao;M. Monier‐Faugere;M. Langub;Z. Geng;T. Nakayama;J. Pike;S. Chernausek;C. Rosen;L. Donahue;H. Malluche;J. Fagin;T. Clemens;T. Clemens
中科院分区：
文献类型：
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作者：
Guisheng Zhao;M. Monier‐Faugere;M. Langub;Z. Geng;T. Nakayama;J. Pike;S. Chernausek;C. Rosen;L. Donahue;H. Malluche;J. Fagin;T. Clemens;T. Clemens
胰岛素样生长因子I （IGF-I）是骨骼的重要生长因子，但其在骨骼中合成代谢活性的调节机制尚不清楚。为了研究体内局部产生的IGF-I在骨中的作用，我们使用人骨钙素启动子将IGF-I靶向表达到转基因小鼠的成骨细胞中。在OC-IGF-I转基因小鼠的成骨细胞中，IGF-I转基因基因高水平表达，血清IGF-I水平或全身生长没有任何变化。3周龄OC-IGF-I转基因小鼠股骨远端骨形成率约为对照组的两倍。6周时，OC-IGF-I转基因小鼠的骨矿物质密度（通过双能x线和定量计算机断层扫描测量）明显高于对照组。组织形态学测量显示OC-IGF-I转基因小鼠的股骨松质骨体积显著增加（30%），但成骨细胞和破骨细胞的总数没有变化。转基因小鼠也表现出骨细胞腔隙占用的增加，表明igf - 1可能延长骨细胞的寿命。我们得出结论，成骨细胞中局部产生的igf - 1主要通过增加常驻成骨细胞的活性来发挥其合成代谢作用。
Insulin-like growth factor I (IGF-I) is an important growth factor for bone, yet the mechanisms that mediate its anabolic activity in the skeleton are poorly understood. To examine the effects of locally produced IGF-I in bone in vivo, we targeted expression IGF-I to osteoblasts of transgenic mice using a human osteocalcin promoter. The IGF-I transgene was expressed in bone osteoblasts in OC-IGF-I transgenic mice at high levels in the absence of any change in serum IGF-I levels, or of total body growth. Bone formation rate at the distal femur in 3-week-old OC-IGF-I transgenic mice was approximately twice that of controls. By 6 weeks, bone mineral density as measured by dual energy x-ray, and quantitative computed tomography was significantly greater in OC-IGF-I transgenic mice compared with controls. Histomorphometric measurements revealed a marked (30%) increase femoral cancellous bone volume in the OC-IGF-I transgenic mice, but no change in the total number of osteoblasts or osteoclasts. Transgenic mice also demonstrated an increase in the osteocyte lacunea occupancy, suggesting that IGF-I may extend the osteocyte life span. We conclude that IGF-I produced locally in bone osteoblasts exerts its anabolic effect primarily by increasing the activity of resident osteoblasts.