Cavolina J M, Evans G L, Harris S A, Zhang M, Westerlind K C, Turner R T
Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Endocrinology. 1997 Apr;138(4):1567-76. doi: 10.1210/endo.138.4.5040.
A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.
使用去卵巢的Fisher 344大鼠进行了为期14天的轨道太空飞行，以确定雌激素缺乏和接近失重对胫骨和桡骨生长以及松质骨转换的综合影响。12只已出现松质骨减少的去卵巢大鼠搭乘哥伦比亚号航天飞机（STS - 62）进行飞行。30只去卵巢大鼠作为地面对照组饲养在地球上：12只饲养在动物饲养舱模块中，12只饲养在动物饲养笼中，6只在发射当天处死以进行基线测量。另外18只未去卵巢的大鼠饲养在动物饲养笼中作为地面对照组：8只作为基线对照处死，其余10只在14天后处死。去卵巢增加了胫腓骨联合处的骨膜骨形成；胫骨近端干骺端次级海绵体中的松质骨吸收和形成；以及对侧胫骨近端干骺端中I型胶原前体α2(1)亚基、骨钙素、转化生长因子-β和胰岛素样生长因子I的信使核糖核酸（mRNA）水平，以及从胫骨和股骨收集的骨膜中胶原亚基的mRNA水平，并减少了松质骨面积。与去卵巢的负重大鼠相比，飞行组的骨膜骨形成、胶原亚基mRNA水平和松质骨面积均有所下降。飞行大鼠的松质骨矿物质沉积率略有下降，但计算得出的骨形成率没有变化。此外，太空飞行对松质骨成骨细胞和破骨细胞周长或骨基质蛋白和信号肽的mRNA水平没有影响。另一方面，从飞行前荧光染料标记保留减少可确定，太空飞行导致骨吸收增加。后一发现表明破骨细胞活性增加。在一项后续的地面实验中，去卵巢大鼠的单侧坐骨神经切断术导致卸载肢体的松质骨丢失超过性腺激素缺乏所致。这种额外的骨丢失通过雌激素替代得以阻止。我们从这些研究中得出结论，雌激素改变了被认为介导骨骼适应机械使用变化的信号肽的表达，同样也改变了骨骼对机械卸载的反应。
