Loss of insulin receptor in osteoprogenitor cells impairs structural strength of bone.
Loss of insulin receptor in osteoprogenitor cells impairs structural strength of bone.
复制标题
骨源细胞中胰岛素受体的丧失会损害骨骼的结构强度。
DOI：
10.1155/2014/703589
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发表时间：
2014
影响因子：
4.3
通讯作者：
Nyman JS
中科院分区：
文献类型：
--
作者：
Thrailkill K;Bunn RC;Lumpkin C Jr;Wahl E;Cockrell G;Morris L;Kahn CR;Fowlkes J;Nyman JS
1 型糖尿病 (T1D) 与骨矿物质密度降低、骨结构缺陷以及随之而来的脆性骨折风险增加有关。这些临床观察结果与 1 型糖尿病动物模型相似，表明 1 型糖尿病的胰岛素减少对骨骼有有害影响。为了进一步研究胰岛素信号对骨骼发育的作用，我们培育了对胰岛素受体 (IR) 进行骨祖细胞选择性 (osterix-Cre) 消融的小鼠，命名为 OIRKO。 OIRKO 小鼠的成骨细胞 IR 降低了 80%。产前消除 IR 不会影响胎儿存活或总体形态。然而，小鼠成骨细胞中IR的丧失导致了出生后生长受限的表型。到 10-12 周龄时，OIRKO 小鼠的股骨变得更细长，骨干皮质更薄，因此在弯曲时整体骨骼强度会下降。仅在雄性小鼠中，还观察到干骺端骨小梁减少，具有更薄且更多的杆状小梁。然而，OIRKO 小鼠并未表现出异常的葡萄糖耐量。 OIRKO 小鼠的骨骼表型似乎比之前报道的骨特异性 IR 敲低模型更严重，这证实了成骨细胞中胰岛素受体的表达对于骨骼的正常发育和结构完整性的维持至关重要。
Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10–12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.
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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
4.8
作者：
CANALIS, EM;DIETRICH, JW;RAISZ, LG
通讯作者：
RAISZ, LG
影响因子：
9.8
作者：
CANALIS, E
通讯作者：
CANALIS, E
影响因子：
3
作者：
Davey, Rachel A.;Clarke, Michele V.;Zajac, Jeffrey D.
通讯作者：
Zajac, Jeffrey D.
影响因子：
16
作者：
Bruning, JC;Michael, MD;Kahn, CR
通讯作者：
Kahn, CR