Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.
Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.
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DOI：
10.1007/s00198-016-3634-3
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Turner RT
中科院分区：
文献类型：
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作者：
Iwaniec UT;Philbrick KA;Wong CP;Gordon JL;Kahler-Quesada AM;Olson DA;Branscum AJ;Sargent JL;DeMambro VE;Rosen CJ;Turner RT
雌性小鼠经常被用作骨质疏松症的临床前模型，但与人类不同的是，小鼠在生长过程中表现出松质骨丢失。小鼠通常被安置在室温(18-23°C)下，这一策略夸大了小鼠和人类之间在体温调节方面的生理差异(强制性的每日异温)和人类(恒温)。这项研究的目的是评估将雌性小鼠安置在中温区(基本能量产生率与热量损失处于平衡的温度范围)是否会改变骨骼生长、周转和微结构。生长(4周龄)雌性C57BL/6J和C3H/HeJ小鼠分别在22℃和32℃下饲养18周。在8-18周龄期间，22°C饲养的C57BL/6J小鼠股骨远端干骺端有62%的松质骨丢失，股骨远端干骺端的骨丢失较少，而32°C饲养的小鼠的松质骨和皮质骨质量没有变化或增加。热中波住房对松质骨的影响并不局限于C57BL/6J小鼠，因为C3H/HeJ小鼠表现出类似的骨骼反应。温中温房对松质骨的有益作用与棕色脂肪组织中Ucp1基因表达降低、骨髓肥胖度增加、骨形成率增加、成骨基因表达水平升高和局部骨吸收减少有关。将雌性小鼠安置在22°C会导致过早的松质骨丢失。未能解释体温调节的物种差异可能会严重混淆利用小鼠作为骨质疏松症临床前模型的研究的解释。
Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18–23°C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 °C or 32°C for up to 18 weeks. C57BL/6J mice housed at 22°C experienced a 62% cancellous bone loss from the distal femur metaphysis during the interval from 8–18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32°C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. Housing female mice at 22°C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies utilizing mice as preclinical models for osteoporosis.