骨钙素对于维持老年小鼠的肌肉量是必要且充分的。
Osteocalcin is necessary and sufficient to maintain muscle mass in older mice.
作者信息
Mera Paula, Laue Kathrin, Wei Jianwen, Berger Julian Meyer, Karsenty Gerard
机构信息
Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
出版信息
Mol Metab. 2016 Jul 16;5(10):1042-1047. doi: 10.1016/j.molmet.2016.07.002. eCollection 2016 Oct.
OBJECTIVE
A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age.
METHODS
We examined muscle mass and strength in mice lacking osteocalcin (Ocn-/-) or its receptor in all cells (Gprc6a-/-) or specifically in myofibers (Gprc6a Mck -/-) as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days. We also examined protein synthesis in WT and Gprc6a-/- mouse myotubes treated with osteocalcin.
RESULTS
We show that osteocalcin signaling in myofibers is necessary to maintain muscle mass in older mice in part because it promotes protein synthesis in myotubes without affecting protein breakdown. We further show that treatment with exogenous osteocalcin for 28 days is sufficient to increase muscle mass of 9-month-old WT mice.
CONCLUSION
This study uncovers that osteocalcin is necessary and sufficient to prevent age-related muscle loss in mice.
目的
肌肉蛋白周转减少进而导致肌肉量减少是衰老的一个标志。由于在小鼠、猴子和人类衰老过程中，骨源性激素骨钙素的循环水平会急剧下降，因此我们在此探究这种激素是否会在小鼠衰老过程中调节肌肉量。
方法
我们检测了缺乏骨钙素（Ocn-/-）或其在所有细胞中的受体（Gprc6a-/-）或特异性在肌纤维中的受体（Gprc6a Mck -/-）的小鼠以及接受外源性骨钙素治疗28天的9月龄野生型（WT）小鼠的肌肉量和力量。我们还检测了用骨钙素处理的野生型和Gprc6a-/-小鼠肌管中的蛋白质合成。
结果
我们发现，肌纤维中的骨钙素信号对于维持老年小鼠的肌肉量是必要的，部分原因是它促进了肌管中的蛋白质合成而不影响蛋白质分解。我们进一步表明，用外源性骨钙素治疗28天足以增加9月龄野生型小鼠的肌肉量。
结论
本研究揭示了骨钙素对于预防小鼠年龄相关的肌肉流失是必要且充分的。
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