Department of Mechanical Engineering, UCB 427, University of Colorado, Boulder, CO 80309, United States of America; BioFrontiers Institute, UCB 596, University of Colorado, Boulder, CO 80309, United States of America.
Department of Mechanical Engineering, UCB 427, University of Colorado, Boulder, CO 80309, United States of America.
Bone. 2021 Oct;151:116021. doi: 10.1016/j.bone.2021.116021. Epub 2021 Jun 2.
The age at which astronauts experience microgravity is a critical consideration for skeletal health and similarly has clinical relevance for musculoskeletal disuse on Earth. While astronauts are extensively studied for bone and other physiological changes, rodent studies enable direct evaluation of skeletal changes with microgravity. Yet, mouse spaceflight studies have predominately evaluated tissues from young, growing mice. We evaluated bone microarchitecture in tibiae and femurs from Young (9-week-old) and Mature (32-weeks-old) female, C57BL/6N mice flown in microgravity for ~2 and ~3 weeks, respectively. Microgravity-induced changes were both compartment- and site-specific. Changes were greater in trabecular versus cortical bone in Mature mice exposed to microgravity (-40.0% Tb. BV/TV vs -4.4% Ct. BV/TV), and bone loss was greater in the proximal tibia as compared to the distal femur. Trabecular thickness in Young mice increased by +25.0% on Earth and no significant difference following microgravity. In Mature mice exposed to microgravity, trabecular thickness rapidly decreased (-24.5%) while no change was detected in age-matched mice that were maintained on Earth. Mature mice exposed to microgravity experienced greater bone loss than Young mice with net skeletal growth. Moreover, machine learning classification models confirmed that microgravity exposure-driven decrements in trabecular microarchitecture and cortical structure occurred disproportionately in Mature than in Young mice. Our results suggest that age of disuse onset may have clinical implications in osteoporotic or other at-risk populations on Earth and may contribute to understanding bone loss patterns in astronauts.
宇航员经历微重力的年龄是骨骼健康的一个关键考虑因素，同样对地球上的肌肉骨骼废用也具有临床意义。虽然宇航员的骨骼和其他生理变化已经得到了广泛的研究，但啮齿动物研究可以直接评估微重力对骨骼的影响。然而，鼠类空间飞行研究主要评估了来自年轻、生长中的老鼠的组织。我们评估了在微重力下飞行约 2 周和 3 周的年轻（9 周龄）和成熟（32 周龄）雌性 C57BL/6N 小鼠的胫骨和股骨的骨微观结构。微重力引起的变化具有腔室和部位特异性。在暴露于微重力的成熟小鼠中，与皮质骨相比，骨小梁的变化更大（-40.0%Tb.BV/TV 与-4.4%Ct.BV/TV），并且与股骨远端相比，胫骨近端的骨丢失更大。在地球上，年轻小鼠的骨小梁厚度增加了 25.0%，而在微重力后没有显著差异。在暴露于微重力的成熟小鼠中，骨小梁厚度迅速减少（-24.5%），而在与微重力暴露的成熟小鼠年龄匹配的保持在地球上的小鼠中没有检测到变化。与年轻小鼠相比，暴露于微重力的成熟小鼠经历了更多的骨质流失，尽管它们的骨骼仍在生长。此外，机器学习分类模型证实，微重力暴露驱动的骨小梁微观结构和皮质结构的减少在成熟小鼠中比在年轻小鼠中不成比例地发生。我们的研究结果表明，在地球上的骨质疏松或其他高危人群中，失用症开始的年龄可能具有临床意义，并且可能有助于理解宇航员的骨质流失模式。
