Preservation of bone mass and structure in hibernating black bears (Ursus americanus) through elevated expression of anabolic genes

Abstract

Physical inactivity reduces mechanical load on the skeleton, which leads to losses of bone mass and strength in non-hibernating mammalian species. Although bears are largely inactive during hibernation, they show no loss in bone mass and strength. To obtain insight into molecular mechanisms preventing disuse bone loss, we conducted a large-scale screen of transcriptional changes in trabecular bone comparing winter hibernating and summer non-hibernating black bears using a custom 12,800 probe cDNA microarray. A total of 241 genes were differentially expressed (P < 0.01 and fold change >1.4) in the ilium bone of bears between winter and summer. The Gene Ontology and Gene Set Enrichment Analysis showed an elevated proportion in hibernating bears of overexpressed genes in six functional sets of genes involved in anabolic processes of tissue morphogenesis and development including skeletal development, cartilage development, and bone biosynthesis. Apoptosis genes demonstrated a tendency for downregulation during hibernation. No coordinated directional changes were detected for genes involved in bone resorption, although some genes responsible for osteoclast formation and differentiation (Ostf1, Rab9a, and c-Fos) were significantly underexpressed in bone of hibernating bears. Elevated expression of multiple anabolic genes without induction of bone resorption genes, and the down regulation of apoptosis-related genes, likely contribute to the adaptive mechanism that preserves bone mass and structure through prolonged periods of immobility during hibernation.