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Int. J. Mol. Sci. 2014, 15(9), 17130-17147; doi:10.3390/ijms150917130

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

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
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 4 July 2014 / Revised: 11 September 2014 / Accepted: 16 September 2014 / Published: 25 September 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
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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Zhang, Z.; Song, C.; Fu, X.; Liu, M.; Li, Y.; Pan, J.; Liu, H.; Wang, S.; Xiang, L.; Xiao, G.G.; Ju, D. High-Dose Diosgenin Reduces Bone Loss in Ovariectomized Rats via Attenuation of the RANKL/OPG Ratio. Int. J. Mol. Sci. 2014, 15, 17130-17147.

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