Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari, 70124, Bari, Italy.
Department of Medicine-DIMED, Internal Medicine 3, University of Padova, 35128, Padova, Italy.
Sci Rep. 2017 Jun 6;7(1):2811. doi: 10.1038/s41598-017-02557-8.
We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass. Here we report that treatment with recombinant Irisin prevented bone loss in hind-limb suspended mice when administered during suspension (preventive protocol) and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks (curative protocol). MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented a dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin protected against muscle mass decline in the hind-limb suspended mice, and maintained the fiber cross-sectional area. Notably, the decrease of myosin type II expression in unloaded mice was completely prevented by r-Irisin administration. Our data reveal for the first time that Irisin retrieves disuse-induced bone loss and muscle atrophy. These findings may lead to development of an Irisin-based therapy for elderly immobile osteoporotic and physically disable patients, and might represent a countermeasure for astronauts subjected to microgravity-induced bone and muscle losses.
我们之前已经证实，运动后从骨骼肌中释放的肌动蛋白（Irisin）在控制骨量方面发挥着核心作用。在这里，我们报告说，在进行后肢悬挂（预防方案）期间给予重组 Irisin 治疗可预防后肢悬挂导致的骨丢失（预防方案），并且当由于 4 周的悬挂期导致骨丢失时，注射重组 Irisin 可诱导骨量恢复（治疗方案）。股骨的 microCT 分析表明，r-Irisin 保留了皮质骨和小梁骨的骨矿物质密度，并防止了小梁骨体积分数的急剧下降。此外，r-Irisin 可防止后肢悬挂的小鼠肌肉质量下降，并维持纤维横截面积。值得注意的是，r-Irisin 的给药完全阻止了未负荷小鼠中肌球蛋白 II 表达的下降。我们的数据首次揭示了 Irisin 可恢复废用性诱导的骨丢失和肌肉萎缩。这些发现可能导致基于 Irisin 的疗法的发展，用于老年骨质疏松和身体残疾患者，并且可能是针对宇航员因微重力引起的骨和肌肉损失的对策。
