Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Language

English

Abstract

Background: In human, a reduction in estrogen has been proposed as one of the key contributing factors for postmenopausal osteoporosis. Rodents are conventional models for studying postmenopausal osteoporosis, but the major limitation is that ovariectomy is needed to mimic the estrogen decline after menopause. Interestingly, in medaka fish (Oryzias latipes), we observed a natural drop in plasma estrogen profile in females during aging and abnormal spinal curvature was apparent in old fish, which are similar to postmenopausal women. It is hypothesized that estrogen associated disorders in bone metabolism might be predicted and prevented by estrogen supplement in aging O. latipes, which could be corresponding to postmenopausal osteoporosis in women. Principal findings: In O. latipes, plasma estrogen was peaked at 8 months old and significantly declined after 10, 11 and 22 months in females. Spinal bone mineral density (BMD) and micro-architecture by microCT measurement progressively decreased and deteriorated from 8 to 10, 12 and 14 months old, which was more apparent in females than the male counterparts. After 10 months old, O. latipes were supplemented with 17α-ethinylestradiol (EE2, a potent estrogen mimic) at 6 and 60 ng/mg fish weight/day for 4 weeks, both reduction in spinal BMD and deterioration in bone micro-architecture were significantly prevented. The estrogenic effect of EE2 in O. latipes was confirmed by significant up-regulation of four key estrogen responsive genes in the liver. In general, bone histomorphometric analyses indicated significantly lowered osteoblasts and osteoclasts numbers and surfaces on vertebrae of EE2-fed medaka. Significance: We demonstrate osteoporosis development associated with natural drop in estrogen level during aging in female medaka, which could be attenuated by estrogen treatment. This small size fish is a unique alternative non-mammalian vertebrate model for studying estrogen-related molecular regulation in postmenopausal skeletal disorders in vivo without ovariectomy.

Publication Date

2014

Source Publication Title

PLoS ONE

Volume

9

Issue

2

Start Page

e88165

Publisher

Public Library of Science

Peer Reviewed

1

Copyright

© 2014 Shanthanagouda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funder

The work described in this paper was supported by grants from the CityU Seed Grant (Project No. 7003024), the University Grants Committee, Area of Excellence Grant (AoE/P-04/04), the State Key Laboratory in Marine Pollution and Hong Kong General Research Fund (HKBU479111).

DOI

10.1371/journal.pone.0088165

ISSN (print)

19326203

ISSN (electronic)

19326203

Large files may be slow to open. For best results, right-click and select "save as..."

Additional Files

JA-5232-26077_suppl.pdf (52 kB)

Share

COinS