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Japanese medaka: a non-mammalian vertebrate model for studying sex and age-related bone metabolism in vivo.

Shanthanagouda AH, Guo BS, Ye RR, Chao L, Chiang MW, Singaram G, Cheung NK, Zhang G, Au DW - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.

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.

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Schematic diagram showing estrogen mediated regulation of bone metabolism based on in vitro and in vivo findings in mammals.FasL: Fatty acid synthatase Ligand, RANKL: Receptor Activator of Nuclear factor Kappa-B Ligand, OPG: Osteoprotegerin. Dark arrows indicate up-regulation; Red arrows indicate down-regulation/apoptosis of osteoclasts. Please refer to the details in
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pone-0088165-g010: Schematic diagram showing estrogen mediated regulation of bone metabolism based on in vitro and in vivo findings in mammals.FasL: Fatty acid synthatase Ligand, RANKL: Receptor Activator of Nuclear factor Kappa-B Ligand, OPG: Osteoprotegerin. Dark arrows indicate up-regulation; Red arrows indicate down-regulation/apoptosis of osteoclasts. Please refer to the details in

Mentions: Several molecular mechanisms have been postulated on estrogen-mediated modulation of bone metabolism, based on in vivo and invitro evidence using mammals, which are summarized in Figure 10[35], [36], [37], [38], [39], [40], [41], [42], [43]. These mechanisms may be conserved in vertebrates from fish to mammals, which warrant further investigations.


Japanese medaka: a non-mammalian vertebrate model for studying sex and age-related bone metabolism in vivo.

Shanthanagouda AH, Guo BS, Ye RR, Chao L, Chiang MW, Singaram G, Cheung NK, Zhang G, Au DW - PLoS ONE (2014)

Schematic diagram showing estrogen mediated regulation of bone metabolism based on in vitro and in vivo findings in mammals.FasL: Fatty acid synthatase Ligand, RANKL: Receptor Activator of Nuclear factor Kappa-B Ligand, OPG: Osteoprotegerin. Dark arrows indicate up-regulation; Red arrows indicate down-regulation/apoptosis of osteoclasts. Please refer to the details in
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921145&req=5

pone-0088165-g010: Schematic diagram showing estrogen mediated regulation of bone metabolism based on in vitro and in vivo findings in mammals.FasL: Fatty acid synthatase Ligand, RANKL: Receptor Activator of Nuclear factor Kappa-B Ligand, OPG: Osteoprotegerin. Dark arrows indicate up-regulation; Red arrows indicate down-regulation/apoptosis of osteoclasts. Please refer to the details in
Mentions: Several molecular mechanisms have been postulated on estrogen-mediated modulation of bone metabolism, based on in vivo and invitro evidence using mammals, which are summarized in Figure 10[35], [36], [37], [38], [39], [40], [41], [42], [43]. These mechanisms may be conserved in vertebrates from fish to mammals, which warrant further investigations.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.

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.

Show MeSH
Related in: MedlinePlus