Gardinier Joseph D, Rostami Niloufar, Juliano Lauren, Zhang Chunbin
Bone and Joint Center, Henry Ford Hospital, Detroit, MI 48202, USA.
Wayne State School of Medicine, Detroit, MI 48202, USA.
Bone Rep. 2018 Jan 12;8:29-37. doi: 10.1016/j.bonr.2018.01.003. eCollection 2018 Jun.
Exercise is a key determinate of fracture risk and provides a clinical means to promote bone formation. However, the efficacy of exercise to increase bone mass declines with age. The purpose of this study was to identify age-related differences in the anabolic response to exercise at the cellular and tissue level. To this end, young (8-weeks of age) and adult (36-weeks of age) male mice were subjected to a moderate exercise regimen of running on a treadmill. As a result, exercise had a significant effect on PTHrP and SOST gene expression during the first week that was dependent upon age. In particular, young mice displayed an increase in PTHrP expression and decrease in SOST expression, both of which remained unaffected by exercise in the adult mice. After 5-weeks of exercise, a significant decrease in the percentage of osteocytes expressing sclerostin at the protein level was found in young mice, but not adult mice. Mechanical testing of the tibia found exercise to have a significant influence on tissue-level mechanical properties, specifically ultimate-stress and modulus that was dependent on age. Adult mice in particular experienced a significant decrease in modulus despite an increase in cortical area and cortical thickness compared to sedentary controls. Altogether, this study demonstrates a shift in the cellular response to exercise with age, and that gains in bone mass at the adult stage fail to improve bone strength.
运动是骨折风险的关键决定因素，并提供了促进骨形成的临床手段。然而，运动增加骨量的功效会随着年龄增长而下降。本研究的目的是确定在细胞和组织水平上，运动的合成代谢反应中与年龄相关的差异。为此，对年轻（8周龄）和成年（36周龄）雄性小鼠进行了在跑步机上跑步的适度运动方案。结果，运动在第一周对甲状旁腺激素相关蛋白（PTHrP）和硬化蛋白（SOST）基因表达有显著影响，且这种影响取决于年龄。具体而言，年轻小鼠的PTHrP表达增加，SOST表达减少，而成年小鼠的这两种表达均不受运动影响。运动5周后，在年轻小鼠中发现表达硬化蛋白的骨细胞百分比在蛋白水平上显著下降，而成年小鼠中未出现这种情况。对胫骨进行力学测试发现，运动对组织水平的力学性能有显著影响，特别是极限应力和模量，且这种影响取决于年龄。与久坐不动的对照组相比，成年小鼠尽管皮质面积和皮质厚度增加，但模量却显著下降。总之，本研究表明随着年龄增长，细胞对运动的反应发生了变化，并且成年期骨量的增加并不能改善骨强度。
