Silvestrini G, Ballanti P, Leopizzi M, Sebastiani M, Berni S, Di Vito M, Bonucci E
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.
J Mol Histol. 2007 Aug;38(4):261-9. doi: 10.1007/s10735-007-9096-3. Epub 2007 Jun 5.
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/mm(2) 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.
硬化素是SOST基因的分泌蛋白产物，主要由骨细胞表达，最近被认为是骨成骨细胞生成的负调节因子。甲状旁腺激素（PTH）的持续升高会降低骨细胞中SOST的表达，而间歇性给予PTH的结果则存在争议。我们研究了间歇性给予PTH对SOST表达和硬化素定位的影响，并将其与对照组进行比较，观察它们在大鼠胫骨的三个不同骨段中的表现：次级小梁干骺端和骨骺骨，以及皮质骨干骨。组织形态计量学结果表明，PTH通过合成代谢作用增强骨转换，这表现为骨吸收变量增加与骨体积/组织体积（BV/TV）、骨小梁厚度（Tb.Th）和骨小梁数量（Tb.N）显著增加以及骨小梁间距（Tb.Sp）降低相关。PTH诱导次级干骺端小梁、骨干骨和骨骺小梁中SOST mRNA和蛋白水平下降。与对照组相比，硬化素免疫阳性骨细胞数量/平方毫米无变化；在对照组和PTH组中，次级干骺端小梁中的硬化素阳性骨细胞均少于其他两个骨区域。干骺端小梁骨中硬化素阳性骨细胞数量较少似乎与该区域具有高重塑率这一事实直接相关。PTH的合成代谢作用与所有三个检测骨段中SOST mRNA和蛋白的下降一致；骨转换的增加支持了SOST在骨形成中的负作用。
