Icariin Stimulates hFOB 1.19 Osteoblast Proliferation and Differentiation via OPG/RANKL Mediated by the Estrogen Receptor

Author(s): Lin-Jun Sun, Chong Li, Xiang-hao Wen, Lu Guo, Zi-Fen Guo, Lan-qing Liao, Yu Guo*

Journal Name: Current Pharmaceutical Biotechnology

Volume 22 , Issue 1 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis.

Methods: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells.

Results: The experimental results show that ICA can stimulate cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA. The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.

Keywords: Icariin, hFOB1.19, osteoblast, proliferation, differentiation, OPG/RANKL.

Suuronen, J.; Sjöblom, S.; Honkanen, R.; Koivumaa-Honkanen, H.; Kröger, H.; Sirola, J.; Rikkonen, T. The relationship of severe health disorders with bone loss, grip strength, and mobility in postmenopausal women - a 15-year follow-up study. Disabil. Rehabil., 2016, 38(14), 1407-1414.
[http://dx.doi.org/10.3109/09638288.2015.1103789] [PMID: 26693679]
Miao, G.; Zhang, Y.; Zhang, Y.; Huang, Y. Effects of icariin on osteogenic differentiation of bone marrow stromal cells in beagle canine. Int. J. Clin. Exp. Pathol., 2017, 10, 8957-8967.
He, J.P.; Feng, X.; Wang, J.F.; Shi, W.G.; Li, H.; Danilchenko, S.; Kalinkevich, A.; Zhovner, M. Icariin prevents bone loss by inhibiting bone resorption and stabilizing bone biological apatite in a hindlimb suspension rodent model. Acta Pharmacol. Sin., 2018, 39(11), 1760-1767.
[http://dx.doi.org/10.1038/s41401-018-0040-8] [PMID: 29891857]
Huang, Z.; Cheng, C.; Wang, J.; Liu, X.; Wei, H.; Han, Y.; Yang, S.; Wang, X. Icariin regulates the osteoblast differentiation and cell proliferation of MC3T3-E1 cells through microRNA-153 by targeting Runt-related transcription factor 2. Exp. Ther. Med., 2018, 15(6), 5159-5166.
[http://dx.doi.org/10.3892/etm.2018.6127] [PMID: 29904399]
Shi, W.; Gao, Y.; Wang, Y.; Zhou, J.; Wei, Z.; Ma, X.; Ma, H. The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts. J. Biologic. Chem., 2017, 292
Zhang, D.; Fong, C.; Jia, Z.; Cui, L.; Yao, X.; Yang, M. Icariin stimulates differentiation and suppresses adipocytic transdifferentiation of primary osteoblasts through estrogen receptor-mediated pathway. Calcif. Tissue Int., 2016, 99(2), 187-198.
[http://dx.doi.org/10.1007/s00223-016-0138-2] [PMID: 27061090]
Wei, Q.; He, M.; Chen, M.; Chen, Z.; Yang, F.; Wang, H.; Zhang, J.; He, W. Icariin stimulates osteogenic differentiation of rat bone marrow stromal stem cells by increasing TAZ expression. Biomed. Pharmacother., 2017, 91, 581-589.
[http://dx.doi.org/10.1016/j.biopha.2017.04.019] [PMID: 28486190]
Ming, L.G.; Lv, X.; Ma, X.N.; Ge, B.F.; Zhen, P.; Song, P.; Zhou, J.; Ma, H.P.; Xian, C.J.; Chen, K.M. The prenyl group contributes to activities of phytoestrogen 8-prenynaringenin in enhancing bone formation and inhibiting bone resorption in vitro. Endocrinology, 2013, 154(3), 1202-1214.
[http://dx.doi.org/10.1210/en.2012-2086] [PMID: 23389955]
Wang, Z.; Wang, D.; Yang, D.; Zhen, W.; Zhang, J.; Peng, S. The effect of icariin on bone metabolism and its potential clinical application. Osteoporos. Int., 2018, 29(3), 535-544.
[http://dx.doi.org/10.1007/s00198-017-4255-1] [PMID: 29110063]
Heo, J.H.; Choi, J.H.; Kim, I.R.; Park, B.S.; Kim, Y.D. Combined treatment with low-level laser and rhbmp-2 promotes differentiation and mineralization of osteoblastic cells under hypoxic stress. Tissue Eng. Regen. Med., 2018, 15(6), 793-801.
[http://dx.doi.org/10.1007/s13770-018-0167-1] [PMID: 30603597]
Ma, B.; Zhang, Q.; Wu, D.; Wang, Y.L.; Hu, Y.Y.; Cheng, Y.P.; Yang, Z.D.; Zheng, Y.Y.; Ying, H.J. Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway. Acta Pharmacol. Sin., 2012, 33(4), 479-489.
[http://dx.doi.org/10.1038/aps.2011.177] [PMID: 22426695]
Chen, H.; Gilbert, L.C.; Lu, X.; Liu, Z.; You, S.; Weitzmann, M.N.; Nanes, M.S.; Adams, J. A new regulator of osteoclastogenesis: Estrogen response element-binding protein in bone. J. Bone Miner. Res., 2011, 26(10), 2537-2547.
[http://dx.doi.org/10.1002/jbmr.456] [PMID: 21773989]
Park, K.; Ju, W.C.; Yeo, J.H.; Kim, J.Y.; Seo, H.S.; Uchida, Y.; Cho, Y. Increased OPG/RANKL ratio in the conditioned medium of soybean-treated osteoblasts suppresses RANKL-induced osteoclast differentiation. Int. J. Mol. Med., 2014, 33(1), 178-184.
[http://dx.doi.org/10.3892/ijmm.2013.1557] [PMID: 24248634]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 22 January, 2020
Page: [168 - 175]
Pages: 8
DOI: 10.2174/1389201021666200123102550
Price: $65

Article Metrics

PDF: 41