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Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

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Abstract:In the present study we provided a morphological and transcriptomic comparison of adult porcine adiposederived stem cells (ADSC) and bone marrow-derived stem cells (BMSC) as they differentiated in vitro towards the osteogenic and adipogenic lineages for up to 4 weeks. The long term goal of this comparison is to assess the possibility of using ADSC as a potential alternative to BMSC as a source of autologous adult stem cells in human therapies. Our data indicated that ADSC can differentiate into osteocytes and adipocytes similar to BMSC but with some differences. During the osteogenic differentiation both cell types went through morphological changes; however, while ADSC formed predominately osteogenic islands (nodules) in the culture dish, BMSC formed a continuous osteogenic sheet of small nodules. Transcriptomic analysis revealed that both cell types responded to the osteogenic induction. However, BGLAP mRNA expression did not increase in ADSC suggesting, together with the percentage area stained observed for Alizarin Red and von Kossa in ADSC, a lesser mineralization of bone matrix in this cell type compared to BMSC. During the adipogenic induction ADSC as well as BMSC were able to achieve the morphological and transcriptome changes characteristic of the adipogenic lineage. After 7 days of differentiation the expression patterns of DGAT2 and ADFP became greater in ADSC versus BMSC, which agreed with the larger lipid droplets formation observed in the ADSC by Oil Red O staining. Our findings represent an important step towards the assessment of using ADSC as an alternative to BMSC in therapeutic applications.