Cold stress during room temperature housing alters skeletal response to simulated microgravity (hindlimb unloading) in growing female C57BL6 mice

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 & DEG;C) or near thermoneutral (32 & DEG;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 & DEG;C. Cancellous osteopenia in distal femur (metaphysis and epiphysis) was noted in HLU mice housed at both temperatures. However, bone loss occurred at 22 & DEG;C, whereas the bone deficit at 32 & DEG;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 & DEG;C. In contrast, fewer osteopenic changes were detected in mice housed at 32 & DEG;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. & COPY; 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

Laboratory mice housed at temperatures outside their thermoneutral zone undergo cold stress and experience premature cancellous bone loss. Studying non-shivering thermogenesis and altered thermogenesis during spaceflight, researchers found that microgravity-induced bone loss in mice may be affected by environmental temperature. The hindlimb unloading (HLU) model was used to simulate microgravity and assess the skeletal response, revealing that housing mice at room temperature led to greater cortical bone loss and cancellous osteopenia compared to those housed at thermoneutral temperature. The findings suggest that environmental temperature plays a role in the skeletal response to simulated microgravity in female mice.