Watson P, Lazowski D, Han V, Fraher L, Steer B, Hodsman A
Department of Medicine, University of Western Ontario, London, Canada.
Bone. 1995 Mar;16(3):357-65. doi: 10.1016/8756-3282(94)00051-4.
In the osteopenic rat model, estrogen deficiency results in increased bone turnover with net bone loss occurring during cancellous modeling. However, estrogen-deficient rats treated with parathyroid hormone (PTH) experience a net gain of bone tissue due to the anabolic effects of PTH. To evaluate the possibility that local insulinlike growth factor I (IGF-I) production modulates the in vivo balance of bone formation and resorption in ovariectomized (OVX) estrogen-deficient rats and in OVX rats treated with PTH, we have studied the expression of IGF-I mRNA in cancellous bone osteoblasts using in situ hybridization techniques. Three-month-old virgin rats were subjected to sham surgery or OVX. Two weeks later, half the OVX rats began treatment with hPTH(1-34), 5 micrograms/100 g body weight, 5 days/week for 4 weeks. All animals were killed at the same time, providing three groups: sham surgery alone; OVX alone; and OVX + PTH. Bone histomorphometry performed in undecalcified sections of tibial metaphysis confirmed that OVX rats had significantly (p < 0.05) increased bone surface formation rates (BFR/BS, micron 3/micron 2/year) with osteopenia while OVX + PTH rats had increased BFR/BS with increased bone volumes compared to sham animals (p < 0.05). Decalcified tissue from all three groups contained immunoreactive IGF-I. Similar tissue sections were hybridized with an 35S-labeled IGF-I antisense riboprobe. Evaluation of the specific signal over cancellous osteoblasts allowed a relative estimate of IGF-I mRNA transcript abundance in the three groups by counting silver grains per osteoblast, corrected for background activity.(ABSTRACT TRUNCATED AT 250 WORDS)
在骨质疏松大鼠模型中，雌激素缺乏导致骨转换增加，在松质骨塑形过程中出现净骨量丢失。然而，用甲状旁腺激素（PTH）治疗的雌激素缺乏大鼠由于PTH的合成代谢作用而出现骨组织净增加。为了评估局部胰岛素样生长因子I（IGF-I）的产生是否调节去卵巢（OVX）雌激素缺乏大鼠和用PTH治疗的OVX大鼠体内骨形成和骨吸收的平衡，我们使用原位杂交技术研究了松质骨成骨细胞中IGF-I mRNA的表达。将3个月大的处女大鼠进行假手术或去卵巢手术。两周后，一半的去卵巢大鼠开始用hPTH(1-34)治疗，剂量为5微克/100克体重，每周5天，共4周。所有动物同时处死，分为三组：单独假手术组；单独去卵巢组；去卵巢+PTH组。对胫骨近端干骺端未脱钙切片进行骨组织形态计量学分析证实，与假手术动物相比，去卵巢大鼠骨表面形成率（BFR/BS，微米³/微米²/年）显著增加（p<0.05），伴有骨质减少，而去卵巢+PTH大鼠的BFR/BS增加，骨体积增加（p<0.05）。三组的脱钙组织均含有免疫反应性IGF-I。用35S标记的IGF-I反义核糖探针与相似的组织切片杂交。通过对每个成骨细胞的银颗粒计数并校正背景活性，评估松质骨成骨细胞上的特异性信号，从而对三组中IGF-I mRNA转录本丰度进行相对估计。（摘要截短于250字）
