Identification of the type IINa+-Pi cotransporter (Npt2) in the osteoclast and the skeletal phenotype of Npt2-/- mice
Identification of the type IINa+-Pi cotransporter (Npt2) in the osteoclast and the skeletal phenotype of Npt2-/- mice
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DOI：
10.1016/s8756-3282(01)00601-9
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发表时间：
2001-11-01
期刊：
影响因子：
4.1
通讯作者：
Hruska, KA
中科院分区：
文献类型：
--
作者：
Gupta, A;Tenenhouse, HS;Hruska, KA
我们之前报道过破骨细胞中表达 II 型磷酸钠 (Na+-Pi) 协同转运蛋白 (Npt2)，并且 Pi 的限制会降低破骨细胞介导的体外骨吸收。我们还证明，Npt2 基因 (Npt2-/-) 纯合子小鼠表现出独特的年龄依赖性骨表型，与显着的低磷血症相关。在本研究中，我们试图鉴定小鼠破骨细胞中的 Npt2 cDNA，并表征 Npt2 基因消融对破骨细胞功能和骨组织形态计量学的影响。我们证明破骨细胞Npt2 cDNA序列与近端肾小管的序列相同，因此不是其同工型或剪接变体。组织形态计量学分析表明，与野生型小鼠相比，Npt2-/- 小鼠在 25 天龄时表现出破骨细胞数量减少和周界侵蚀。此外，尽管25日龄的Npt2-/-小鼠干骺端小梁数量减少，但由于小梁宽度增加，骨小梁体积正常。 115 日龄时，与野生型同窝小鼠相比，Npt2-/- 小鼠的破骨细胞指数持续下降。然而，矿化和成骨细胞表面以及骨形成率增加，尽管小梁数量仍然减少，但小梁骨体积高于野生型小鼠。这些数据证明了年轻 Npt2-/- 小鼠中破骨细胞活性和小梁发育之间的联系，并表明对 Npt2 缺乏的年龄相关适应在破骨细胞和成骨细胞功能以及骨形成中是明显的。 (C) 2001 年，Elsevier Science Inc. 保留所有权利。
We previously reported that a type II sodium phosphate (Na+-Pi) cotransporter (Npt2) protein is expressed in osteoclasts and that Pi limitation decreases osteoclast-mediated bone resorption in vitro. We also demonstrated that mice homozygous for the disrupted Npt2 gene (Npt2-/-) exhibit a unique age-dependent bone phenotype that is associated with significant hypophosphatemia. In the present study, we sought to identify the Npt2 cDNA in mouse osteoclasts and characterize the impact of Npt2 gene ablation on osteoclast function and bone histomorphometry. We demonstrate that the osteoclast Npt2 cDNA sequence is identical to that of the proximal renal tubule and, thus, not an isoform or splice variant thereof. Histomorphometric analysis revealed that, at 25 days of age, Npt2-/- mice exhibited a reduction in osteoclast number and eroded perimeters, relative to wildtype mice. Moreover, although the number of metaphyseal trabeculae was reduced in 25-day-old Npt2-/- mice, trabecular bone volume was normal due to increased trabecular width. At 115 days of age, the decrease in osteoclast index persisted in Npt2-/- mice relative to wild-type littermates. However, mineralizing and osteoblast surfaces and bone formation rates were increased, and, although trabecular number was still reduced, trabecular bone volume was higher than that of wild-type mice. These data demonstrate a link between osteoclast activity and trabecular development in young Npt2-/- mice, and suggest that an age-related adaptation to Npt2 deficiency is apparent in osteoclast and osteoblast function and bone formation. (C) 2001 by Elsevier Science Inc. All rights reserved.