Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
Xi'an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
Int J Mol Sci. 2020 Feb 13;21(4):1259. doi: 10.3390/ijms21041259.
: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. : The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. : We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (), collagen type 1 alpha-1()) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. : The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.
: 鸢尾素是一种新型的运动诱导肌因子，它被证明可以介导运动对骨质疏松症的有益作用。微重力是宇航员在长期太空飞行中骨内稳态的主要威胁，导致骨形成减少。: 后肢去负荷小鼠模型和随机位置机分别用于模拟体内和体外的微重力。: 我们证明，不仅骨形成和成骨细胞分化减少，而且纤维连接蛋白 III 型结构域包含 5（Fdnc5；鸢尾素前体）的表达也在模拟微重力下下调。此外，较低剂量的重组鸢尾素（r-irisin）（1 nM）可促进原代成骨细胞中成骨标志物基因（碱性磷酸酶（）、胶原类型 1 alpha-1()）的表达、ALP 活性和钙沉积，对成骨细胞增殖没有明显影响。此外，r-irisin 可恢复模拟微重力引起的成骨细胞分化减少。我们还发现，r-irisin 增加 β-连环蛋白的表达，并部分中和模拟微重力引起的 β-连环蛋白表达下降。此外，β-连环蛋白过表达也可部分减轻模拟微重力引起的成骨细胞分化减少。: 本研究首次表明，r-irisin 通过增加 β-连环蛋白的表达，可积极调节模拟微重力下的成骨细胞分化，这可能揭示了一种新的机制，并为预防微重力引起的骨质流失和肌肉萎缩提供了一种策略。
