Jagger C J, Chow J W, Chambers T J
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
J Clin Invest. 1996 Nov 15;98(10):2351-7. doi: 10.1172/JCI119047.
We used a model whereby mechanical stimulation induces bone formation in rat caudal vertebrae, to test the effect of estrogen on this osteogenic response. Unexpectedly, estrogen administered daily throughout the experiments (8-11 d) suppressed, and ovariectomy enhanced, mechanically induced osteogenesis. Osteogenesis was unaffected by the resorption-inhibitor pamidronate, suggesting that the suppression of bone formation caused by estrogen was not due to suppression of resorption. We found that estrogen did not significantly reduce the proportion of osteocytes that were induced by mechanical stimulation to express c-fos and IGF-I mRNA; and estrogen suppressed mechanically induced osteogenesis whether administration was started 24 h before or 24 h after loading. This suggests that estrogen acts primarily not on the strain-sensing mechanism itself, but on the osteogenic response to signals generated by strain-sensitive cells. We also found that when estrogen administration was started 3 d after mechanical stimulation, by which time osteogenesis is established, estrogen augmented the osteogenic response. This data is consistent with in vitro evidence for estrogen responsiveness in two phenotypically distinct bone cell types: stromal cells, whose functional activities are suppressed, and osteoblasts, which are stimulated, by estrogen.
我们采用了一种模型，即通过机械刺激诱导大鼠尾椎骨形成骨组织，以测试雌激素对这种成骨反应的影响。出乎意料的是，在整个实验过程（8 - 11天）中每日给予雌激素会抑制机械诱导的成骨作用，而卵巢切除术则会增强这种作用。成骨作用不受吸收抑制剂帕米膦酸盐的影响，这表明雌激素导致的骨形成抑制并非由于吸收的抑制。我们发现，雌激素并未显著降低因机械刺激而被诱导表达c - fos和IGF - I mRNA的骨细胞比例；并且无论在加载前24小时还是加载后24小时开始给予雌激素，它都会抑制机械诱导的成骨作用。这表明雌激素主要不是作用于应变传感机制本身，而是作用于对应变敏感细胞产生的信号的成骨反应。我们还发现，当在机械刺激后3天开始给予雌激素时，此时成骨作用已经确立，雌激素会增强成骨反应。该数据与体外实验证据一致，即在两种表型不同的骨细胞类型中雌激素具有反应性：基质细胞，其功能活性被雌激素抑制；以及成骨细胞，其被雌激素刺激。
