Differentiation and Proliferation of Periosteal Osteoblast Progenitors Are Differentially Regulated by Estrogens and Intermittent Parathyroid Hormone Administration
Differentiation and Proliferation of Periosteal Osteoblast Progenitors Are Differentially Regulated by Estrogens and Intermittent Parathyroid Hormone Administration
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DOI：
10.1210/en.2008-0369
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发表时间：
2008-11-01
期刊：
影响因子：
4.8
通讯作者：
Kousteni, Stavroula
中科院分区：
文献类型：
--
作者：
Ogita, Mami;Rached, Marie Therese;Kousteni, Stavroula
骨膜现在被广泛认为是性类固醇和间歇性甲状旁腺激素给药的稳态和治疗靶点。雌激素抑制而甲状旁腺素促进骨膜扩张的机制尚不清楚。在这份报告中，我们表明，间歇性PTH（1-34）促进骨膜成骨细胞前体分化的碱性磷酸酶的表达或活性的刺激，以及骨形态发生蛋白2（BMP-2）和Wnt通路的目标证明。相比之下，17 β-雌二醇（E-2）本身没有影响。然而，它减弱了PTH或BMP-2诱导的原代骨膜成骨细胞祖细胞的分化。卵巢切除小鼠间歇性给予PTH可诱导骨膜中BMP-2靶点Smad 1/5/8快速磷酸化。替代剂量的E-2本身没有影响，但抑制PTH诱导的Smad 1/5/8磷酸化。与其刺激骨膜成骨细胞分化的作用相反，PTH在体外和体内促进并随后抑制骨膜成骨细胞祖细胞的增殖。E-2促进细胞增殖，减弱PTH的抗增殖作用。这两种激素保护骨膜成骨细胞免受各种促凋亡剂诱导的凋亡。这些观察结果表明，PTH和雌激素对骨膜的不同影响是由于对早期骨膜成骨细胞祖细胞的募集产生相反的作用。间歇性PTH通过ERK、BMP和Wnt依赖性信号通路促进骨膜来源的间充质祖细胞向成骨细胞分化。雌激素促进早期成骨细胞祖细胞的增殖，但通过成骨剂如PTH或BMP-2抑制其分化。（内分泌学149：5713-5723，2008）
The periosteum is now widely recognized as a homeostatic and therapeutic target for actions of sex steroids and intermittent PTH administration. The mechanisms by which estrogens suppress but PTH promotes periosteal expansion are not known. In this report, we show that intermittent PTH(1-34) promotes differentiation of periosteal osteoblast precursors as evidenced by the stimulation of the expression or activity of alkaline phosphatase as well as of targets of the bone morphogenetic protein 2 (BMP-2) and Wnt pathways. In contrast, 17 beta-estradiol (E-2) had no effect by itself. However, it attenuated PTH- or BMP-2-induced differentiation of primary periosteal osteoblast progenitors. Administration of intermittent PTH to ovariectomized mice induced rapid phosphorylation of the BMP-2 target Smad1/5/8 in the periosteum. A replacement dose of E-2 had no effect by itself but suppressed PTH- induced phosphorylation of Smad1/5/8. In contrast to its effects to stimulate periosteal osteoblast differentiation, PTH promoted and subsequently suppressed proliferation of periosteal osteoblast progenitors in vitro and in vivo. E-2 promoted proliferation and attenuated the antiproliferative effect of PTH. Both hormones protected periosteal osteoblasts from apoptosis induced by various proapoptotic agents. These observations suggest that the different effects of PTH and estrogens on the periosteum result from opposing actions on the recruitment of early periosteal osteoblast progenitors. Intermittent PTH promotes osteoblast differentiation from periosteum-derived mesenchymal progenitors through ERK-, BMP-, and Wnt- dependent signaling pathways. Estrogens promote proliferation of early osteoblast progenitors but inhibit their differentiation by osteogenic agents such as PTH or BMP-2. (Endocrinology 149: 5713-5723, 2008)