Osteocalcin plasticity and enhanced colocalization with Gprc6A may contribute to musculoskeletal maintenance in...

Hibernating mammals provide a natural model for investigating mechanisms of resistance to disuse-induced musculoskeletal degeneration. However, the molecular pathways enabling muscle and bone preservation during prolonged inactivity remain insufficiently defined. This study examined the temporal dynamics of osteocalcin and its receptor G protein-coupled receptor family C group 6 member A (Gprc6A) across hibernation states in Daurian ground squirrels (Spermophilus dauricus) to elucidate potential mechanisms of musculoskeletal maintenance during torpor-arousal cycles.

Hindlimb muscle and bone mass, along with tibial bone microstructure, were quantitatively assessed at key hibernation phases. Serum osteocalcin concentrations and expression profiles of osteocalcin and Gprc6A were evaluated by western blotting and immunofluorescent colocalization analyses.

Musculoskeletal mass and tibial microstructure exhibited only minor changes across hibernation periods (P > 0.05). Tibial osteocalcin expression decreased significantly during torpor compared to the summer active phase but was restored during interbout arousal. In the soleus (SOL) and extensor digitorum longus (EDL) muscles, osteocalcin expression was markedly up-regulated during interbout arousal relative to torpor (P < 0.05). Gprc6A expression in the EDL also increased significantly during interbout arousal compared to summer and torpor phases. Enhanced colocalization of osteocalcin and Gprc6A was observed in both tibial bone and EDL muscle during torpor (P < 0.05).

Daurian ground squirrels exhibited remarkable musculoskeletal resilience during prolonged hibernation, maintaining structural integrity despite extended inactivity. Oscillatory expression of osteocalcin and Gprc6A during arousal phases, combined with sustained ligand-receptor colocalization during torpor, may constitute a coordinated endocrine-musculoskeletal adaptation that preserves tissue function during hibernation.