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Article

High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio

by
Zhiguo Zhang
1,†,
Changheng Song
1,†,
Xiaowei Fu
2,
Meijie Liu
1,
Yan Li
1,
Jinghua Pan
1,
Hong Liu
1,
Shaojun Wang
1,
Lihua Xiang
1,
Gary Guishan Xiao
3,* and
Dahong Ju
1,*
1
Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China
2
Clinical Medical College of Chinese and Western Medicine, Shaanxi University of Chinese Medicine, Xi'an 712046, China
3
Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE 68131, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(9), 17130-17147; https://doi.org/10.3390/ijms150917130
Submission received: 4 July 2014 / Revised: 11 September 2014 / Accepted: 16 September 2014 / Published: 25 September 2014
(This article belongs to the Section Biochemistry)
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Abstract

The aim of this study was to evaluate effect of diosgenin (DG) on rats that had osteoporosis-like features induced by ovariectomy (OVX). Seventy-two six-month-old female Wistar rats were subjected to either ovariectomy (n = 60) or Sham operation (SHAM group, n = 12). Beginning at one week post-ovariectomy, the OVX rats were treated with vehicle (OVX group, n = 12), estradiol valerate (EV group, n = 12), or DG at three doses (DG-L, -M, -H group, n = 12, respectively). After a 12-week treatment, administration of EV or DG-H inhibited OVX-induced weight gain, and administration of EV or DG-H or DG-M had a significantly uterotrophic effect. Bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated by immunohistochemistry and in situ hybridization. Our results show that DG at a high dose (DG-H) had a significant anti-osteoporotic effect compared to OVX control. DG-H treatment down-regulated expression of RANKL and up-regulated expression of OPG significantly in tibia from OVX rats compared to control, and thus lowered the RANKL/OPG ratio. This suggests that the anti-osteoporotic effect of DG might be associated with modulating the RANKL/OPG ratio and DG had potential to be developed as alternative therapeutic agents of osteoporosis induced by postmenopause.
Keywords: diosgenin; bone loss; ovariectomized rats; osteoprotegerin; receptor activator of nuclear factor kappa-B ligand diosgenin; bone loss; ovariectomized rats; osteoprotegerin; receptor activator of nuclear factor kappa-B ligand
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MDPI and ACS Style

Zhang, Z.; Song, C.; Fu, X.; Liu, M.; Li, Y.; Pan, J.; Liu, H.; Wang, S.; Xiang, L.; Xiao, G.G.; et al. High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio. Int. J. Mol. Sci. 2014, 15, 17130-17147. https://doi.org/10.3390/ijms150917130

AMA Style

Zhang Z, Song C, Fu X, Liu M, Li Y, Pan J, Liu H, Wang S, Xiang L, Xiao GG, et al. High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio. International Journal of Molecular Sciences. 2014; 15(9):17130-17147. https://doi.org/10.3390/ijms150917130

Chicago/Turabian Style

Zhang, Zhiguo, Changheng Song, Xiaowei Fu, Meijie Liu, Yan Li, Jinghua Pan, Hong Liu, Shaojun Wang, Lihua Xiang, Gary Guishan Xiao, and et al. 2014. "High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio" International Journal of Molecular Sciences 15, no. 9: 17130-17147. https://doi.org/10.3390/ijms150917130

APA Style

Zhang, Z., Song, C., Fu, X., Liu, M., Li, Y., Pan, J., Liu, H., Wang, S., Xiang, L., Xiao, G. G., & Ju, D. (2014). High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio. International Journal of Molecular Sciences, 15(9), 17130-17147. https://doi.org/10.3390/ijms150917130

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