Article

Icariin prevents bone loss by inhibiting bone resorption and stabilizing bone biological apatite in a hindlimb suspension rodent model

Authors: Jin-peng He1, Xiu Feng1,2, Ju-fang Wang1, Wen-gui Shi1,3, He Li1, Sergei Danilchenko4, Aleksei Kalinkevich4, Mykhailo Zhovner4
1 Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 73000, China
2 School of Pharmacy, Lanzhou University, Lanzhou 730000, China
3 University of Chinese Academy of Sciences, Beijing 100049, China
4 Institute of Applied Physics, National Academy of Sciences of Ukraine, Sumy 40000, Ukraine
Correspondence to: Ju-fang Wang: jufangwang@impcas.ac.cn,
DOI: 10.1038/s41401-018-0040-8
Received: 24 August 2017
Accepted: 28 February 2018
Advance online: 11 June 2018

Abstract

Bone loss induced by microgravity is a substantial barrier to humans in long-term spaceflight. Recent studies have revealed that icariin (ICA) can attenuate osteoporosis in postmenopausal women and ovariectomized rats. However, whether ICA can protect against microgravity-induced bone loss remains unknown. In this study, the effects of ICA on a hindlimb suspension rodent model were investigated. Two-month-old female Wistar rats were hindlimb suspended and treated with ICA (25 mg·kg−1·d−1, i.g.) or a vehicle for 4 weeks (n = 6). The bone mass density of the hindlimbs was analyzed using dual-energy X-ray absorptiometry and micro-CT. mRNA expression of osteogenic genes in the tibia and the content of bone metabolism markers in serum were measured using qRT-PCR and ELISA, respectively. The bone mineral phase was analyzed using X-ray diffraction and atomic spectrometry. The results showed that ICA treatment significantly rescued the hindlimb suspension-induced reduction in bone mineral density, trabecular number and thickness, as well as the increases in trabecular separation and the structure model index. In addition, ICA treatment recovered the decreased bone-related gene expression, including alkaline phosphatase (ALP), bone glaprotein (BGP), and osteoprotegerin/receptor activator of the NF-κB ligand ratio (OPG/RANKL), in the tibia and the decreased bone resorption marker TRACP-5b levels in serum caused by simulated microgravity. Notably, ICA treatment restored the instability of bone biological apatite and the metabolic disorder of bone mineral elicited by simulated microgravity. These results demonstrate that ICA treatment plays osteoprotective roles in bone loss induced by simulated microgravity by inhibiting bone resorption and stabilizing bone biological apatite.
Keywords: icariin; simulated microgravity; bone loss; hindlimb suspension; apatite; bone resorption

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