title: Japanese medaka: a non-mammalian vertebrate model for studying sex and age-related bone metabolism in vivo.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors: Admane H
authors: AH
authors: Shanthanagouda
authors: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors: Bao-Sheng
authors: BS
authors: Guo
authors: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors: Rui R
authors: RR
authors: Ye
authors: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors: Liang
authors: L
authors: Chao
authors: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors: Michael W L
authors: MW
authors: Chiang
authors: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors: Gopalakrishnan
authors: G
authors: Singaram
authors: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors: Napo K M
authors: NK
authors: Cheung
authors: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors: Ge
authors: G
authors: Zhang
authors: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
authors: Doris W T
authors: DW
authors: Au
mesh_terms: D000375:Aging; D000818:Animals; D015519:Bone Density / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004967:Estrogens / Q000097:blood; D004997:Ethinyl Estradiol / Q000737:chemistry; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D009990:Oryzias; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000503:physiopathology; D012737:Sex Factors; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D004967:Estrogens; D004997:Ethinyl Estradiol