Icariin ameliorates dexamethasone‑induced bone deterioration in an experimental mouse model via activation of microRNA‑186 inhibition of cathepsin K

Ma,Yongsheng; Yang,Hao; Huang,Junqing

doi:10.3892/mmr.2017.8065

Icariin ameliorates dexamethasone‑induced bone deterioration in an experimental mouse model via activation of microRNA‑186 inhibition of cathepsin K

Authors:
- Yongsheng Ma
- Hao Yang
- Junqing Huang
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Affiliations: Department of Orthopaedics, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450002, P.R. China
Published online on: November 15, 2017 https://doi.org/10.3892/mmr.2017.8065
Pages: 1633-1641
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate bone deterioration in glucocorticoid‑induced osteoporosis (GIOP) mice, and the anti‑osteoporosis effect and underlying molecular mechanism of icariin. Dexamethasone (DSM) treatment was demonstrated to facilitate the induction of hypercalciuria in GIOP mice. Icariin treatment reversed the dexamethasone (DXM)‑induced disequilibrium of calcium homeostasis and bone resorption, and increased serum alkaline phosphatase, tartrate resistant acid phosphatase, osteocalcin and deoxypyridinoline. Haematoxylin and eosin staining revealed an increase in disconnections and separation in the trabecular bone network of the tibial proximal metaphysis, in the GIOP group. Icariin treatment reversed the DXM‑induced trabecular deleterious effects, and stimulated bone remodeling in GIOP mice. Furthermore, the results demonstrated that the mRNA and protein expression of cathepsin K were significantly increased in GIOP mice, compared with the control group. Icariin treatment may suppress the expression of cathepsin K in the tibia of GIOP mice. The levels of microRNA (miR)‑186 were markedly reduced in the tibia of GIOP mice compared with control group; however, this was inhibited by icariin treatment. Bioinformatics analysis demonstrated that miR‑186 regulates cathepsin K via binding to the upstream 3'‑untranslated region. Furthermore, transfection with miR‑186 mimics resulted in inhibition of cathepsin K expression, whereas miR‑186 inhibitors facilitated cathepsin K expression in osteoclasts. In conclusion, the present study demonstrated the protective effects of icariin against bone deteriorations in the experimental GIOP mice, and the underlying mechanism was mediated, at least partially, via activation of miR‑186‑mediated suppression of cathepsin K. These results provide evidence to support the use of icariin as a therapeutic approach in the management of glucocorticoid‑induced bone loss, and the disequilibrium of calcium homeostasis.

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