Iwaniec U T, Philbrick K A, Wong C P, Gordon J L, Kahler-Quesada A M, Olson D A, Branscum A J, Sargent J L, DeMambro V E, Rosen C J, Turner R T
Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA.
Center for Healthy Aging Research, Oregon State University, Corvallis, OR, 97331, USA.
Osteoporos Int. 2016 Oct;27(10):3091-101. doi: 10.1007/s00198-016-3634-3. Epub 2016 May 17.
Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies.
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 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 to 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.
室温饲养（22°C）会导致雌性小鼠的松质骨过早流失。将小鼠饲养在热中性温度（32°C）下可防止骨流失。小鼠和人类的产热情况有显著差异，标准室温饲养所诱导的轻度冷应激可能会给临床前研究引入一个未被认识到的混杂变量。
雌性小鼠常被用作骨质疏松症的临床前模型，但与人类不同的是，小鼠在生长过程中会出现松质骨流失。小鼠通常饲养在室温（18 - 23°C）下，这种策略会夸大小鼠（强制性每日变温动物）和人类（恒温动物）在体温调节方面的生理差异。本研究的目的是评估将雌性小鼠饲养在热中性环境（能量产生的基础速率与热量损失达到平衡的温度范围）是否会改变骨骼生长、周转和微观结构。
将生长中的（4周龄）雌性C57BL/6J和C3H/HeJ小鼠分别饲养在22°C或32°C环境中长达18周。
在8至18周龄期间，饲养在22°C的C57BL/6J小鼠股骨远端干骺端的松质骨流失了62%，股骨远端骨骺的骨流失较少，而饲养在32°C的小鼠的松质骨和皮质骨质量未变或增加。热中性饲养对松质骨的影响并不局限于C57BL/6J小鼠，因为C3H/HeJ小鼠也表现出类似的骨骼反应。热中性饲养对松质骨的有益作用与棕色脂肪组织中Ucp1基因表达降低、骨髓脂肪增多、骨形成率提高、成骨基因表达水平升高以及局部骨吸收减少有关。
将雌性小鼠饲养在22°C会导致松质骨过早流失。未能考虑到体温调节方面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结果的解释。
