Bone adaptation to mechanical loading in mice is affected by circadian rhythms

Area of Science:

• Bone Biology
• Circadian Rhythms
• Mechanobiology

Background:

• Physical forces are essential for bone health.
• Daily timing affects physiology due to circadian rhythms.
• Bone's response to mechanical stimuli may be circadian-regulated.

Purpose of the Study:

• To investigate if circadian rhythms modulate bone's adaptive response to mechanical loading.
• To determine if the timing of mechanical loading impacts gene expression and bone formation.

Main Methods:

• Mice tibiae were analyzed for diurnal expression of clock and bone-related genes.
• In vivo mechanical loading was applied at different times of day (ZT2 vs. ZT14).
• Microcomputed tomography (microCT) and histomorphometry assessed bone formation over two weeks.

Main Results:

• Core clock genes and Wnt inhibitors (Sost, Dkk1) showed diurnal expression in cortical bone.
• Mechanical loading timing altered Sost and Dkk1 expression.
• Loading during the active phase (ZT14) enhanced endocortical bone formation compared to the resting phase (ZT2).

Conclusions:

• Circadian clocks influence the bone's response to mechanical loading.
• The timing of mechanical stimuli is critical for optimizing adaptive bone formation.
• This suggests potential for chronomodulated exercise interventions for bone health.