Martin Stephen A, Philbrick Kenneth A, Wong Carmen P, Olson Dawn A, Branscum Adam J, Jump Donald B, Marik Charles K, DenHerder Jonathan M, Sargent Jennifer L, Turner Russell T, Iwaniec Urszula T
Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA.
Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA.
Endocr Connect. 2019 Nov;8(11):1455-1467. doi: 10.1530/EC-19-0359.
Mice are a commonly used model to investigate aging-related bone loss but, in contrast to humans, mice exhibit cancellous bone loss prior to skeletal maturity. The mechanisms mediating premature bone loss are not well established. However, our previous work in female mice suggests housing temperature is a critical factor. Premature cancellous bone loss was prevented in female C57BL/6J mice by housing the animals at thermoneutral temperature (where basal rate of energy production is at equilibrium with heat loss). In the present study, we determined if the protective effects of thermoneutral housing extend to males. Male C57BL/6J mice were housed at standard room temperature (22°C) or thermoneutral (32°C) conditions from 5 (rapidly growing) to 16 (slowly growing) weeks of age. Mice housed at room temperature exhibited reductions in cancellous bone volume fraction in distal femur metaphysis and fifth lumbar vertebra; these effects were abolished at thermoneutral conditions. Mice housed at thermoneutral temperature had higher levels of bone formation in distal femur (based on histomorphometry) and globally (serum osteocalcin), and lower global levels of bone resorption (serum C-terminal telopeptide of type I collagen) compared to mice housed at room temperature. Thermoneutral housing had no impact on bone marrow adiposity but resulted in higher abdominal white adipose tissue and serum leptin. The overall magnitude of room temperature housing-induced cancellous bone loss did not differ between male (current study) and female (published data) mice. These findings highlight housing temperature as a critical experimental variable in studies using mice of either sex to investigate aging-related changes in bone metabolism.
小鼠是研究与衰老相关的骨质流失常用的模型，但与人类不同的是，小鼠在骨骼成熟之前就会出现松质骨流失。介导过早骨质流失的机制尚未完全明确。然而，我们之前在雌性小鼠身上的研究表明，饲养温度是一个关键因素。通过将雌性C57BL/6J小鼠饲养在热中性温度（即能量产生的基础速率与热量损失达到平衡的温度）下，可以防止过早的松质骨流失。在本研究中，我们确定热中性饲养的保护作用是否也适用于雄性小鼠。将雄性C57BL/6J小鼠从5周龄（快速生长阶段）到16周龄（缓慢生长阶段）分别饲养在标准室温（22°C）或热中性温度（32°C）条件下。饲养在室温下的小鼠，其股骨远端干骺端和第五腰椎的松质骨体积分数降低；而在热中性条件下，这些影响则被消除。与饲养在室温下的小鼠相比，饲养在热中性温度下的小鼠，其股骨远端（基于组织形态计量学）和整体（血清骨钙素）的骨形成水平更高，而整体骨吸收水平（血清I型胶原C末端肽）更低。热中性饲养对骨髓脂肪含量没有影响，但会导致腹部白色脂肪组织和血清瘦素水平升高。室温饲养引起的松质骨流失的总体程度在雄性（本研究）和雌性（已发表数据）小鼠之间没有差异。这些发现突出了饲养温度是使用任何性别的小鼠研究与衰老相关的骨代谢变化的研究中的一个关键实验变量。
