Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation.
Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation.
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DOI：
10.1016/j.bbrc.2011.11.019
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发表时间：
2011-12-16
影响因子：
3.1
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Li Z;Zeng F;Mitchell AD;Kim YS;Wu Z;Yang J
骨形态发生蛋白11（Bone Morphogenetic Protein 11，BMP 11）是骨骼发育的关键调控蛋白。BMP 11前肽已显示在体外拮抗GDF 11活性。为了探索BMP 11前肽在体内骨骼形成中的作用，我们产生了具有BMP 11前肽cDNA特异性过表达的转基因小鼠。在我们之前的报告中，小鼠显示第七颈椎转化为胸椎。目前，转基因小鼠的进一步表征表明，在16.5 dpc的转基因胎儿与野生型同窝仔相比，在胼胝体的骨化显着增强。双能X线骨密度测定结果显示，10周龄时，转基因小鼠的骨矿含量和骨密度显著高于同窝野生型小鼠（P<0.05）。通过组织学分析测量的相对骨小梁体积在转基因小鼠中与它们的野生型同窝小鼠相比显著增加。转基因小鼠骨形成的增强似乎是由于成骨细胞活性增加的结果，因为转基因胎儿中4种成骨细胞标志物-α 1 1型胶原、骨钙素、碱性磷酸酶和phex的表达显著高于其野生型同窝仔。这些结果表明，BMP 11前肽的过度表达通过增加成骨细胞功能来刺激骨形成。
Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression of BMP11 propeptide cDNA. The mice showed a transformation of the seventh cervical vertebra into a thoracic vertebra in our previous report. Presently, further characterizations of the transgenic mice indicated that ossification in calvatia was dramatically enhanced in transgenic fetuses at 16.5 dpc in comparison with their wild-type littermates. At 10 weeks of age, bone mineral content and bone mineral density were significantly (P<0.05) higher in transgenic mice than that in their wild-type littermates based on dual energy X-ray absorptiometry analysis. The relative trabecular bone volume measured by histological analysis was dramatically increased in transgenic mice compared with their wild- type littermates. The enhanced bone formations in the transgenic mice appear to result from increase osteoblast activities as the expressions of four osteoblast markers-α 1 type 1 collagen, osteocalcin, alkaline phosphatase and phex were significantly higher in transgenic fetuses than that in their wild-type littermates. These results suggest that over-expression of BMP11 propeptide stimulates bone formation by increasing osteoblast cell functions.