C - Michigan Technological University

favorable since differentiation would utilize metabolic energy, which bears mustconserve during hibernation. In fact, although osteoblast activity remains balanced withosteoclast activity, activities of both cell types dramatically decrease during hibernation,as is seen in histomorphometric data [18, 20] and serum levels of BSALP (Table 5.3).Finally, regression analysis was used to determine what hormones may beresponsible for reduced osteoblast differentiation and caspase-3/7 activation duringhibernation. Serum levels of the neuropeptide NPY increase in the serum of hibernatingbears, and are inversely correlated with caspase-3/7 response to apoptotic threat inosteoblasts (Table 5.4). Although there are no known studies demonstrating arelationship between NPY and osteoblast caspase-3 and -7 response, NPY is known tosuppress osteoblast differentiation [246]. Furthermore, NPY is negatively correlated toserum BSALP, suggesting a possible relationship between NPY and bone turnover inthe bear. Another potential effector of differentiation is adiponectin, which decreases inthe serum of hibernating bears and is positively correlated to caspase-3/7 response toapoptotic threat in osteoblasts (Table 5.4). Again, although there are no known studiesdemonstrating a relationship between adiponectin and caspase-3 and -7 response,adiponectin has been shown to stimulate osteoblast proliferation, differentiation, andexpression of BSALP in cultured osteoblasts [202]. Adiponectin levels are positivelycorrelated to serum BSALP in the bears, suggesting that it, too, could be regulatingturnover during hibernation.Bears have a unique ability to maintain bone despite prolonged mechanicalunloading (i.e. hibernation). The aim of this study was to demonstrate that a factor in theserum of hibernating bears would protect cultured osteoblasts from apoptosis. Such aprevention of osteoblast and osteocyte apoptosis in the bones of hibernating bears mayhelp maintain bone during this period of disuse. Compared to cells cultured in activebear serum, osteoblasts cultured in serum from hibernating bears had reduced caspase-3 and -7 activity and a higher percentage of living cells after 6 hours of serum starvation.These findings suggest that the osteoblast response to apoptotic stimulus may bereduced during hibernation. This effect did not appear to be PKA dependent or stronglysensitive to pertussis toxin. Based upon regression analysis, two possible hormones areNPY and adiponectin. Both hormones have an impact on osteoblast differentiation,82