Hibernators have adapted a physiological mechanism allowing them to undergo long periods of inactivity without experiencing bone loss. However, the biological mechanisms that prevent bone loss are unknown. Previous studies found meaningful changes, between active and hibernating marmots, in the endocannabinoid system of many tissues, including bone. Cannabinoid receptors (CB1 and CB2) have divergent localization in bone. CB1 is predominately found on sympathetic nerve terminals, while CB2 is more abundant on bone cells and their progenitors. This study aimed to determine the contribution of innervation on endocannabinoid regulation of bone properties in hibernating (during torpor) and non-hibernating yellow-bellied marmots. Neurectomy, a model for disuse osteoporosis, was performed unilaterally in both hibernating and active marmots. Endocannabinoid concentrations were measured in bone marrow, cortical, and trabecular regions from fourth metatarsals of both hindlimbs using microflow chromatography-tandem quadrupole mass spectrometry. Trabecular bone architectural properties of fifth metatarsals were evaluated using micro-computed tomography. There were ligand-specific increases with neurectomy in active, but not hibernating, marmots. Trabecular bone architectural properties were not affected by neurectomy during hibernation, but did show some minor negative changes in active marmots. These findings suggest protection from bone loss in hibernating rodents is peripherally rather than centrally regulated. Furthermore, findings suggest even active marmots with normal metabolism are partially protected from disuse induced bone loss compared to laboratory rodents. Understanding the mechanism hibernators use to maintain bone density may guide development for novel bone loss prevention therapies.

中文翻译：

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神经切除和冬眠对土拨鼠（Marmota flaviventris）的骨骼特性和内源性大麻素系统的影响。

冬眠者采用了一种生理机制，可以长时间不活动，而不会出现骨质流失。但是，防止骨丢失的生物学机制尚不清楚。先前的研究发现，在活跃和冬眠的土拨鼠之间，包括骨骼在内的许多组织的内源性大麻素系统都发生了有意义的变化。大麻受体（CB1和CB2）在骨骼中的分布不同。CB1主要存在于交感神经末梢，而CB2则更多存在于骨细胞及其祖细胞中。这项研究的目的是确定神经支配对冬眠（在por鼠期间）和非冬眠土拨鼠土拨鼠对骨骼特性的内源性大麻素调节的贡献。在冬眠和活动土拨鼠中都单方面进行了神经切除术，该模型是废用骨质疏松症的模型。使用微流色谱-串联四极杆质谱仪测量两个后肢第四meta骨的骨髓，皮质和小梁区域的内源性大麻素浓度。使用微计算机断层扫描技术评估第五architectural骨的小梁骨建筑特性。在活跃但非冬眠的土拨鼠中，神经切除术具有配体特异性增加。冬眠期间，神经切除术不会影响小梁的骨结构特性，但在活动土拨鼠中确实显示出一些轻微的负面变化。这些发现表明，保护冬眠啮齿动物免受骨质流失的保护是外围而非中央调节的。此外，研究结果表明，与实验室啮齿类动物相比，即使具有正常新陈代谢的活跃土拨鼠也能部分保护其免于因滥用而引起的骨质流失。