Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an, 710069, People's Republic of China.
Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, 229# North Taibai Road, Xi'an, 710069, People's Republic of China.
J Comp Physiol B. 2021 Jul;191(4):793-814. doi: 10.1007/s00360-021-01375-9. Epub 2021 May 18.
To determine that differential bone remodeling mechanism (especially Wnt signaling) in hindlimb unloaded rats and hibernating Daurian ground squirrels, the bone microstructure, mechanical properties, and expression levels of bone remodeling related proteins and key proteins of Wnt/β-catenin signaling were analyzed in this study. The thickness of cortical and trabecular bone was decreased in femur of hindlimb unloaded rats, while it was maintained in femur of hibernating ground squirrels. Interestingly, the ultimate bending energy and ultimate normalized displacement were reduced and the bending rigidity was increased in tibia of hibernating ground squirrels. Besides, the protein level of Runx2 was decreased in femur and tibia of unloaded rats, while it was maintained in tibia and even increased in femur of hibernating ground squirrels. The protein levels of RANKL and MMP-9 were increased in femur and tibia in unloaded rats, while they were maintained in both femur and tibia of hibernating ground squirrels. The protein level of GSK-3β was increased in femur and tibia of unloaded rats, while it was maintained in both femur and tibia of hibernating ground squirrels. The phospho-β-catenin expression was increased in both femur and tibia of unloaded rats, while it was only decreased in femur, but maintained in tibia of hibernating ground squirrels. In conclusion, the femur and tibia in hindlimb unloaded rats showed obvious bone loss, while they mitigated disuse-induced bone loss in hibernating ground squirrels, involving differential protein expression of key molecules in bone remodeling. In comparison with hindlimb unloaded rats, promoting osteoblast differentiation through activating canonical GSK-3β/β-catenin signaling involving Runx2 might be an adaptation to natural disuse in femur of hibernating Daurian ground squirrels. However, there was no statistical change in the protein levels of bone formation related proteins, GSK-3β and phospho-β-catenin in tibia of hibernating Daurian ground squirrels.
为了确定后肢去负荷大鼠和冬眠达乌尔黄鼠骨重塑机制（特别是 Wnt 信号）的差异，本研究分析了骨微结构、力学性能以及骨重塑相关蛋白和 Wnt/β-catenin 信号关键蛋白的表达水平。后肢去负荷大鼠股骨皮质骨和松质骨厚度降低，而冬眠达乌尔黄鼠股骨骨厚度维持不变。有趣的是，冬眠达乌尔黄鼠胫骨的最大弯曲能和最大归一化位移降低，弯曲刚度增加。此外，去负荷大鼠股骨和胫骨中 Runx2 蛋白水平降低，而冬眠达乌尔黄鼠胫骨中 Runx2 蛋白水平维持不变，甚至股骨中 Runx2 蛋白水平增加。去负荷大鼠股骨和胫骨中 RANKL 和 MMP-9 蛋白水平增加，而冬眠达乌尔黄鼠股骨和胫骨中均维持不变。去负荷大鼠股骨和胫骨中 GSK-3β 蛋白水平增加，而冬眠达乌尔黄鼠股骨和胫骨中均维持不变。去负荷大鼠股骨和胫骨中磷酸化 β-catenin 表达增加，而冬眠达乌尔黄鼠仅股骨中磷酸化 β-catenin 表达降低，胫骨中维持不变。总之，后肢去负荷大鼠的股骨和胫骨表现出明显的骨丢失，而冬眠达乌尔黄鼠减轻了骨丢失，涉及骨重塑关键分子的差异蛋白表达。与后肢去负荷大鼠相比，通过激活涉及 Runx2 的经典 GSK-3β/β-catenin 信号促进成骨细胞分化可能是冬眠达乌尔黄鼠股骨对自然去负荷的一种适应。然而，冬眠达乌尔黄鼠胫骨中与骨形成相关的蛋白、GSK-3β 和磷酸化 β-catenin 的蛋白水平没有统计学变化。
