Intermittent PTH Administration Stimulates Pre-Osteoblastic Proliferation Without Leading to Enhanced Bone Formation in Osteoclast-Less c-fos-/- Mice
Intermittent PTH Administration Stimulates Pre-Osteoblastic Proliferation Without Leading to Enhanced Bone Formation in Osteoclast-Less c-fos-/- Mice
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DOI：
10.1359/jbmr.090413
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发表时间：
2009-09-01
影响因子：
6.2
通讯作者：
Amizuka, Norio
中科院分区：
文献类型：
--
作者：
de Freitas, Paulo Henrique Luiz;Li, Minqi;Amizuka, Norio
本研究旨在研究间歇性 PTH 治疗后成骨细胞的行为和超微结构，并试图阐明破骨细胞在介导 PTH 驱动的骨合成代谢中的作用。对野生型和c-fos(-/-)小鼠间歇性给予PTH后，进行免疫组织化学、组织形态学、超微结构和统计学检查。在PTH处理的野生型小鼠中，与骨形成相关的结构和动力学参数有所增加，而在破骨细胞缺陷的c-fos(-/-)小鼠中，组间没有显着差异。在野生型和基因敲除小鼠中，PTH 给药导致碱性磷酸酶和 BrdU 双阳性细胞数量显着增加，表明前成骨细胞增殖活跃。超微结构检查显示出两种主要的前成骨细胞亚型：一种富含内质网（ER），即hypER细胞，另一种具有较少且分散的ER，即misER细胞。在野生型小鼠中施用 PTH 后，后者构成了最丰富的前成骨细胞表型。在 c-fos(-/-) 小鼠中，misER 细胞存在于骨表面，但似乎并未积极产生骨基质。一些misER细胞被证明对EphB4呈阳性，并且最终在施用PTH的野生型小鼠中观察到与破骨细胞相当接近。我们得出的结论是，c-fos(-/-) 小鼠中破骨细胞的缺乏可能会阻碍 PTH 驱动的骨合成代谢，并且破骨细胞的存在可能是间歇性 PTH 给药后观察到的完全成骨细胞分化和增强骨形成所必需的。骨矿工研究杂志 2009；24：1586-1597。 2009年4月27日在线发布；号码：10.1359/JBMR.090413
This study aimed to investigate the behavior and ultrastructure of osteoblastic cells after intermittent PTH treatment and attempted to elucidate the role of osteoclasts on the mediation of PTH-driven bone anabolism. After administering PTH intermittently to wildtype and c-fos(-/-) mice, immunohistochemical, histomorphometrical, ultrastructural, and statistical examinations were performed. Structural and kinetic parameters related to bone formation were increased in PTH-treated wildtype mice, whereas in the osteoclast-deficient c-fos(-/-) mice, there were no significant differences between groups. In wildtype and knockout mice, PTH administration led to significant increases in the number of cells double-positive for alkaline phosphatase and BrdU, suggesting active pre-osteoblastic proliferation. Ultrastructural examinations showed two major pre-osteoblastic subtypes: one rich in endoplasmic reticulum (ER), the hypER cell, and other with fewer and dispersed ER, the misER cell. The latter constituted the most abundant preosteoblastic phenotype after PTH administration in the wildtype mice. In c-fos(-/-) mice, misER cells were present on the bone surfaces but did not seem to be actively producing bone matrix. Several misER cells were shown to be positive for EphB4 and were eventually seen rather close to osteoclasts in the PTH-administered wildtype mice. We concluded that the absence of osteoclasts in c-fos(-/-) mice might hinder PTH-driven bone anabolism and that osteoclastic presence may be necessary for full osteoblastic differentiation and enhanced bone formation seen after intermittent PTH administration. J Bone Miner Res 2009;24:1586-1597. Published online on April 27, 2009; doi: 10.1359/JBMR.090413