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Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and protein in rat bone

机译:间歇性甲状旁腺激素(PTH)给药对大鼠骨骼SOST mRNA和蛋白的影响

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摘要

Sclerostin, the secreted protein product of the SOST gene, which is mainly expressed by osteocytes, has recently been proposed as a negative regulator of bone osteoblastogenesis. Chronic elevation of PTH reduces SOST expression by osteocytes, while controversial results have been obtained by intermittent PTH administration. We have investigated the effects of intermittently administered PTH on SOST expression and sclerostin localization, comparing them with those of controls, as they appeared in three different bone segments of rat tibia: secondary trabecular metaphyseal and epiphyseal bone, and cortical diaphyseal bone. The histomorphometric results demonstrate that PTH enhances bone turnover through anabolic effects, as shown by the association of increased bone resorption variables with a significant rise in BV/TV, Tb.Th and Tb.N and a fall in Tb.Sp. PTH induces a SOST mRNA and protein fall in secondary metaphyseal trabeculae, diaphyseal bone and in epiphyseal trabeculae. Numbers of sclerostin immunopositive osteocytes/mm2 show no change, compared with controls; there are fewer sclerostin-positive osteocytes in secondary metaphyseal trabeculae than in the other two bone areas, both in the control and PTH groups. The low numbers of sclerostin-positive osteocytes in the metaphyseal trabecular bone seem to be directly related to the fact that this area displays a high remodeling rate. The anabolic effects of PTH are in line with the fall of SOST mRNA and protein in all the three bone segments examined; the rise of bone turnover supports a negative role of SOST in bone formation.
机译:硬化蛋白,SOST基因的分泌蛋白产物,主要由骨细胞表达,最近被提出作为骨成骨细胞生成的负调节剂。 PTH的慢性升高会降低骨细胞的SOST表达,而间歇性PTH给药已获得了有争议的结果。我们研究了间歇性施用PTH对SOST表达和硬化素定位的影响,并将它们与对照的影响进行了比较,因为它们出现在大鼠胫骨的三个不同骨节中:继发性小梁干phy端和epi骨以及皮质干phy端骨。组织形态计量学结果表明,PTH通过合成代谢作用增强了骨转换,如骨吸收变量增加与BV / TV,Tb.Th和Tb.N的显着升高以及Tb.Sp.的下降相关。 PTH在继发的干phy端小梁,干dia端骨和epi小梁中诱导SOST mRNA和蛋白质下降。与对照相比,硬化素免疫阳性骨细胞/ mm2 的数量没有变化。在对照组和PTH组中,继发性干phy端小梁中硬化蛋白阳性骨细胞的数量少于其他两个骨区域。干phy端小梁骨中硬化素阳性骨细胞的数量低似乎与该区域显示出较高的重塑率这一事实直接相关。 PTH的合成代谢作用与所检查的所有三个骨段中SOST mRNA和蛋白质的下降相符。骨转换的增加支持了SOST在骨形成中的负作用。

著录项

  • 来源
    《Journal of Molecular Histology》 |2007年第4期|261-269|共9页
  • 作者单位

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologica Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologica Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologica Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologica Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologica Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologia Generale Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

    Dipartimento di Medicina Sperimentale e Patologia Sezioni di Anatomia Patologica Università degli Studi di Roma “La Sapienza” Azienda Policlinico Umberto I Viale Regina Elena 324 00161 Rome Italy;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Sclerostin; Osteocytes; Parathyroid hormone; Osteoblastogenesis; Bone histomorphometry;

    机译:硬化素;骨细胞;甲状旁腺激素;成骨细胞;骨组织形态学;

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