Mechanism of action of estrogen on intramembranous bone formation: regulation of osteoblast differentiation and activity.
Mechanism of action of estrogen on intramembranous bone formation: regulation of osteoblast differentiation and activity.
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DOI：
10.1210/endo.131.2.1639030
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发表时间：
1992-08
期刊：
影响因子：
4.8
通讯作者：
R. Turner;P. Backup;P. Sherman;E. Hill;G. Evans;T. Spelsberg
中科院分区：
文献类型：
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作者：
R. Turner;P. Backup;P. Sherman;E. Hill;G. Evans;T. Spelsberg
在去卵巢（OVX）和雌激素治疗的OVX大鼠的颅骨中进行动态骨组织形态计量学、[3 H]胸苷放射自显影和骨基质蛋白和胰岛素样生长因子-I（IGF-I）的北方分析。用己烯雌酚（DES）治疗OVX大鼠2周可降低颅骨骨膜中的骨膜矿物质沉积率、成骨细胞数量和成骨细胞大小。DES处理还减少了细胞周期S期的前成骨细胞的数量，这表明成骨细胞数量的减少部分是由于抑制了骨祖细胞的增殖。卵巢切除术后1周，I型胶原蛋白（胶原蛋白）前α 2（I）亚基、骨钙素和骨连接素的mRNA水平略有增加，IGF-I的mRNA水平大幅增加。DES治疗导致骨粘连蛋白、骨钙素和IGF-I的mRNA水平快速下降（3 h）。相反，胶原蛋白的mRNA水平在短期DES治疗后几乎没有变化。子宫和肝脏分别作为阳性和阴性对照组织，DES对OVX大鼠IGF-I mRNA水平的影响;激素治疗后，子宫中的mRNA水平升高，肝脏中的mRNA水平降低。我们从这些研究中得出结论，雌激素通过抑制成骨细胞的分化和活性来减少骨膜骨形成。此外，IGF-I和骨基质蛋白mRNA水平的下调先于动态骨组织形态计量学的变化。
Dynamic bone histomorphometry, [3H]thymidine radioautography, and Northern analysis for bone matrix proteins and insulin-like growth factor-I (IGF-I) were performed in calvariae of ovariectomized (OVX) and estrogen-treated OVX rats. Treatment of OVX rats with diethylstilbestrol (DES) for 2 weeks reduced the periosteal mineral apposition rate, osteoblast number, and osteoblast size in calvarial periosteum. DES treatment also reduced the number of preosteoblasts in the S phase of the cell cycle, suggesting that the decrease in osteoblast number was due in part to inhibition of proliferation of osteoprogenitor cells. One week after ovariectomy, there were small increases in mRNA levels for pre pro-alpha 2 (I) subunit of type I collagen (collagen), osteocalcin, and osteonectin and a large increase in the mRNA level for IGF-I. DES treatment resulted in rapid decreases (3 h) in the mRNA levels for osteonectin, osteocalcin, and IGF-I. In contrast, mRNA levels for collagen were virtually unchanged after short term DES treatment. Uterus and liver served as positive and negative control tissues, respectively, for the effects of DES on IGF-I mRNA levels in OVX rats; mRNA levels were increased in uterus and decreased in liver after hormone treatment. We conclude from these studies that estrogen reduces periosteal bone formation by inhibiting both the differentiation and activity of osteoblasts. Furthermore, down-regulation of mRNA levels for IGF-I and bone matrix proteins precedes the changes in dynamic bone histomorphometry.