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Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

by Zhihao Chen 1,2,3,4,†, Yan Zhang 1,2,3,4,†, Fan Zhao 1,2,3,4, Chong Yin 1,2,3,4, Chaofei Yang 1,2,3,4, Xue Wang 1,2,3,4, Zixiang Wu 1,2,3,4, Shujing Liang 1,2,3,4, Dijie Li 1,2,3,4, Xiao Lin 1,2,3,4, Ye Tian 1,2,3,4, Lifang Hu 1,2,3,4,*, Yu Li 1,2,3,4 and Airong Qian 1,2,3,4,*
1
Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
2
Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
3
Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
4
NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(4), 1259; https://doi.org/10.3390/ijms21041259
Received: 26 January 2020 / Revised: 10 February 2020 / Accepted: 12 February 2020 / Published: 13 February 2020
Background: 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. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: 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 (Alp), collagen type 1 alpha-1(ColIα1)) 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. Conclusions: 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. View Full-Text
Keywords: irisin; simulated microgravity; osteoblast differentiation; β-catenin; bone loss irisin; simulated microgravity; osteoblast differentiation; β-catenin; bone loss
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Chen, Z.; Zhang, Y.; Zhao, F.; Yin, C.; Yang, C.; Wang, X.; Wu, Z.; Liang, S.; Li, D.; Lin, X.; Tian, Y.; Hu, L.; Li, Y.; Qian, A. Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression. Int. J. Mol. Sci. 2020, 21, 1259.

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