Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential
Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential
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DOI：
10.1016/j.bone.2007.02.007
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发表时间：
2007-06-01
期刊：
影响因子：
4.1
通讯作者：
Nakamura, Toshitaka
中科院分区：
文献类型：
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作者：
Otomo, Hajime;Sakai, Akinori;Nakamura, Toshitaka
为了阐明Fms样酪氨酸激酶-1（Flt-1）信号在骨动力学中的作用，我们检查了6、9和16周龄的C57 BL/6 J小鼠，这些小鼠的flt 1酪氨酸激酶结构域基因（flt 1（TK-/-））被破坏，并与年龄匹配的野生型（flt 1（TK+/+））小鼠进行了比较。动态组织形态计量学分析证实，与inf 1（TK+/+）小鼠相比，flt 1（TK-/-）小鼠近端胫骨骨小梁的矿化表面（MS/BS）、矿物质沉积率（MAR）和骨形成率（BFR/BS）值显著降低。与flt 1（TK+/+）小鼠相比，flt 1（-/-）小鼠的骨小梁体积（BV/TV）值也显著降低。flt 1（TK-/-）小鼠的破骨细胞表面积（Oc.S/BS）和破骨细胞数（Oc.N/BS）均低于flt 1（TK+/+）小鼠。flt 1（TK-/-）小鼠股骨弯曲载荷值显著降低。此外，与flt 1（TK+/+）小鼠相比，flt 1（TK-/-）小鼠的血清骨钙素显著降低。此外，flt-1（TK-/-）小鼠骨髓基质细胞矿化能力明显降低，提示flt-1（TK-/-）小鼠的骨小梁体积低于flt 1（TK+/+）小鼠，这为通过Flt-1酪氨酸激酶结构域的血管内皮生长因子信号通路参与成骨细胞的发育提供了有力的证据。(c)2007年爱思唯尔公司All rights reserved.
To clarify the role of Fms-like tyrosine kinase-1 (Flt-1) signaling in bone dynamics, we examined C57BL/6J mice, aged 6, 9 and 16 weeks, with disruption of the flt1 tyrosine kinase domain gene (flt1(TK-/-)) and compared with age-matched wild-type (flt1(TK+/+)) mice. Dynamic histomorphometric analysis confirmed a significant decrease in the values of mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) in the trabecular bone of the proximal tibiae of flt1(TK-/-) mice compared with those inf1(TK+/+) mice. The value of trabecular bone volume (BV/TV) was also significantly reduced in flt1(-/-) mice compared with that in,flt1(TK+/+) mice. The values of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS) in flt1(TK-/-) mice were somewhat lower than those in flt1(TK+/+) mice. The values of bending load of the femur significantly decreased in flt1(TK-/-) mice. In addition, serum osteocalcin significantly decreased in flt1(TK-/-) mice compared with those in flt1(TK+/+) mice. Furthermore, there was a significant decreased mineralization of bone marrow stromal cultures from flt1(TK-/-) mice.These findings demonstrate that flt1(TK-/-) mice show lower trabecular bone volume than flt1(TK+/+) mice, providing powerful evidence that vascular endothelial growth factor signal pathway through the Flt-1 tyrosine kinase domain could be implicated in osteoblast development. (c) 2007 Elsevier Inc. All rights reserved.