![]() It is likely bone remodeling is suppressed in bears during hibernation to conserve energy, and that bone resorption and formation are balanced to preserve eucalcemia during anuria 5, 8. Serum calcium concentration is preserved in hibernating bears when they do not drink, eat, urinate or defecate (i.e., excrete calcium) 5, 7. This is normally countered by osteoblasts rebuilding bone (i.e., putting calcium ions back into bone matrix) 6. Calcium ions are readily exchanged between blood and bone by the continuous bone remodeling process in which osteoclasts resorb bone releasing calcium from the bone extracellular matrix, which can be taken up into blood vessels. Most (99%) of calcium in the body is stored in bone as hydroxyapatite mineral crystals. The maintenance of normal calcium concentrations in blood, extracellular fluid, and cytosol is critical to maintaining essential physiologic functions needed to survive hibernation, such as heart beat and skeletal muscle contraction for respiration and thermogenesis. However, bone is also an organ that plays an essential role in integrative organismal physiology by maintaining calcium homeostasis. Bone metabolism is a metabolically expensive process that is substantially reduced during hibernation 3, 4, 5. Suppressed metabolism for the conservation of metabolic energy is the hallmark of hibernation 1, 2. Mitochondrial oxidation was likely up-regulated by transcriptionally induced AMPK/PGC1α pathway, an upstream stimulator of mitochondrial function. Additionally, we revealed significant and coordinated transcriptional induction of gene sets involved in aerobic energy production including fatty acid beta oxidation, tricarboxylic acid cycle, oxidative phosphorylation, and mitochondrial metabolism. In contrast, no significant enrichment indicating directional changes in gene expression was detected in the gene sets of bone formation and osteoblast signaling in hibernating bears. These findings are consistent with previous histological findings and likely contribute to the preservation of bone during the immobility of hibernation. Gene set enrichment analysis showed a coordinated down-regulation of genes involved in bone resorption, osteoclast differentiation and signaling, and apoptosis during hibernation. To identify transcriptional changes that underlie molecular mechanisms preventing disuse osteoporosis, we conducted a large-scale gene expression screening in the trabecular bone and bone marrow, comparing hibernating and summer active bears through sequencing of the transcriptome. In contrast, hibernating bears show no bone loss over the prolonged periods (4–6 months) of immobility during winter, which suggests that they have adaptive mechanisms to preserve bone mass. ![]() Physical inactivity leads to losses of bone mass and strength in most mammalian species.
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