Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA.
Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA.
Biochimie. 2023 Jul;210:61-70. doi: 10.1016/j.biochi.2022.12.009. Epub 2022 Dec 28.
Laboratory mice are typically housed at temperatures below the thermoneutral zone for the species, resulting in cold stress and premature cancellous bone loss. Furthermore, mice are more dependent upon non-shivering thermogenesis to maintain body temperature during spaceflight, suggesting that microgravity-induced bone loss may be due, in part, to altered thermogenesis. Consequently, we assessed whether housing mice at room temperature modifies the skeletal response to simulated microgravity. This possibility was tested using the hindlimb unloading (HLU) model to mechanically unload femora. Humeri were also assessed as they remain weight bearing during HLU. Six-week-old female C57BL6 (B6) mice were housed at room temperature (22 °C) or near thermoneutral (32 °C) and HLU for 2 weeks. Compared to baseline, HLU resulted in cortical bone loss in femur, but the magnitude of reduction was greater in mice housed at 22 °C. Cancellous osteopenia in distal femur (metaphysis and epiphysis) was noted in HLU mice housed at both temperatures. However, bone loss occurred at 22 °C, whereas the bone deficit at 32 °C was due to failure to accrue bone. HLU resulted in cortical and cancellous bone deficits (compared to baseline) in humeri of mice housed at 22 °C. In contrast, fewer osteopenic changes were detected in mice housed at 32 °C. These findings support the hypothesis that environmental temperature alters the skeletal response to HLU in growing female mice in a bone compartment-specific manner. Taken together, species differences in thermoregulation should be taken into consideration when interpreting the skeletal response to simulated microgravity.
实验小鼠通常被饲养在低于物种热中性区的温度下，导致冷应激和骨小梁提前丢失。此外，小鼠在太空飞行中更依赖于非颤抖性产热来维持体温，这表明微重力引起的骨丢失可能部分是由于产热改变。因此，我们评估了将小鼠饲养在室温下是否会改变骨骼对模拟微重力的反应。使用后肢去负荷（HLU）模型来机械地去负荷股骨来检验这种可能性。由于在 HLU 期间仍承受体重，因此还评估了肱骨。将 6 周龄的雌性 C57BL6（B6）小鼠饲养在室温（22°C）或接近热中性（32°C）下，并进行 HLU 2 周。与基线相比，HLU 导致股骨皮质骨丢失，但在 22°C 饲养的小鼠中，减少的幅度更大。在两种温度下饲养的 HLU 小鼠均出现了远端股骨（干骺端和骨骺）的松质骨骨质疏松症。然而，在 22°C 时发生了骨丢失，而在 32°C 时的骨缺陷是由于未能积累骨。HLU 导致了 22°C 饲养的小鼠的皮质骨和松质骨缺失（与基线相比）。相比之下，在 32°C 饲养的小鼠中，检测到的骨质疏松变化较少。这些发现支持了这样一种假设，即环境温度以特定于骨腔室的方式改变了生长中雌性小鼠对 HLU 的骨骼反应。总之，在解释模拟微重力对骨骼的反应时，应该考虑物种在体温调节方面的差异。
