Strain-dependent variations in the response of cancellous bone to ovariectomy in mice
Strain-dependent variations in the response of cancellous bone to ovariectomy in mice
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DOI：
10.1359/jbmr.060402
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发表时间：
2006-07-01
影响因子：
6.2
通讯作者：
Wronski, Thomas J.
中科院分区：
文献类型：
--
作者：
Iwaniec, Urszula T.;Yuan, Dawn;Wronski, Thomas J.
简介：卵巢切除（OVX）大鼠是绝经后骨质疏松症最广泛使用的临床前啮齿动物模型。然而，包括骨质疏松症在内的骨骼疾病的潜在机制主要在小鼠中进行了探索。本研究的目的是评估小鼠（129 P3和C5713 L/6近交系和他们的F-2杂交后代，B6129 PF 2），通常用于基因敲除和过表达的研究，其潜在的绝经后骨loss.Materials和方法的临床前模型：小鼠OVX或假手术在4个月的年龄，并在手术后1或3个月杀死。腰椎和股骨远端进行histomorphometric assessment.Results：小鼠在两个菌株和F-2杂交（将被称为应变的摘要的其余部分）失去了椎体松质骨OVX后，骨体积（BV/TV）分别为20%和27%，在手术后1个月和3个月，分别降低。仅在129 P3品系中，OVX后1个月松质骨BV/TV的降低与破骨细胞表面的增加相关。成骨细胞表面增加了20%，OVX在手术后1个月和3个月，无论小鼠应变。然而，骨形成率没有改变OVX在任何小鼠品系。与腰椎相反，在三种小鼠品系中，股骨远端对OVX反应的松质骨丢失不同。在B6129 PF 2小鼠品系中，OVX对股骨远端BV/TV无显著影响。在C57 BL/6品系中，OVX在术后1个月降低了松质骨BV/TV，但在术后3个月未降低，而129 P3小鼠的股骨远端BV/TV在术后3个月降低。在C5713 L/6品系中，破骨细胞表面在任一时间点均不受OVX影响，但在129 P3品系中，在手术后1个月时破骨细胞表面增加了116%。成骨细胞表面增加与OVX在手术后1个月，无论应变，而骨形成率没有改变OVX在任何时间点在任何strain.Conclusions：松质骨丢失的幅度和细胞指数增加骨转换响应OVX不同的小鼠应变和骨骼网站，但在一般情况下，不太明显，不太一致，比在Sprague-Dawley大鼠。尽管小鼠模型将继续提供对骨量和骨转换的遗传影响的见解，但在使用129 P3和C5713 L/6小鼠及其F-2杂交小鼠作为绝经后骨丢失和骨质疏松症潜在疗法的临床前测试模型时应谨慎。
Introduction: The ovariectomized (OVX) rat is the most widely used preclinical rodent model for postmenopausal osteoporosis. However, the underlying mechanisms of bone disorders, including osteoporosis, have been explored predominantly in the mouse. The purpose of this study was to evaluate mice (129P3 and C5713L/6 inbred strains and their F-2 hybrid offspring, B6129PF2), commonly used for gene knockout and overexpression studies, for their potential as preclinical models of postmenopausal bone loss.Materials and Methods: The mice were OVX or sham-operated at 4 months of age and killed at 1 or 3 months after surgery. Lumbar vertebrae and distal femora were subjected to histomorphometric assessment.Results: Mice in the two strains and the F-2 hybrids (will be referred to as strain for the remainder of the abstract) lost vertebral cancellous bone after OVX; bone volume (BV/TV) was 20% and 27% lower at 1 and 3 months after surgery, respectively. The decreased cancellous BV/TV was associated with an increase in osteoclast surface at I month after OVX in the 129P3 strain only. Osteoblast surface was increased by 20% with OVX at both 1 and 3 months after surgery, irrespective of mouse strain. However, bone formation rate was not altered by OVX in any of the mouse strains. In contrast to the lumbar vertebrae, cancellous bone loss in response to OVX differed in the distal femur among the three mouse strains. OVX had no significant effect on distal femur BV/TV in the B6129PF2 mouse strain. In the C57BL/6 strain, cancellous BV/TV was reduced by OVX at I month after surgery but not at 3 months after surgery, whereas distal femur BV/TV in 129P3 mice was reduced at 3 months after surgery. Osteoclast surface was not affected by OVX at either time-point in the C5713L/6 strain, but was increased by 116% at I month after surgery in the 129P3 strain. Osteoblast surface was increased with OVX at 1 month after surgery, irrespective of strain, whereas bone formation rate was not altered by OVX at either time-point in any of the strains.Conclusions: The magnitude of cancellous bone loss and cellular indices of increased bone turnover in response to OVX varied with mouse strain and skeletal site, but in general, were less pronounced and less consistent than in the Sprague-Dawley rat. Although mouse models will continue to provide insights into genetic influences on bone mass and turnover, caution should be exercised when using 129P3 and C5713L/6 mice, and their F-2 hybrids, as models for postmenopausal bone loss and preclinical testing of potential therapies for osteoporosis.