Chondroitin sulfate-E mediates estrogen-induced osteoanabolism

Osteoporosis is an age-related disorder of bone remodeling in which bone resorption outstrips bone matrix deposition. Although anticatabolic agents are frequently used as first-line therapies for osteoporosis, alternative anabolic strategies that can enhance anabolic, osteogenic potential are active...

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Autores principales: Koike, Toshiyasu, Mikami, Tadahisa, Shida, Miharu, Habuchi, Osami, Kitagawa, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355730/
https://www.ncbi.nlm.nih.gov/pubmed/25759206
http://dx.doi.org/10.1038/srep08994
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author Koike, Toshiyasu
Mikami, Tadahisa
Shida, Miharu
Habuchi, Osami
Kitagawa, Hiroshi
author_facet Koike, Toshiyasu
Mikami, Tadahisa
Shida, Miharu
Habuchi, Osami
Kitagawa, Hiroshi
author_sort Koike, Toshiyasu
collection PubMed
description Osteoporosis is an age-related disorder of bone remodeling in which bone resorption outstrips bone matrix deposition. Although anticatabolic agents are frequently used as first-line therapies for osteoporosis, alternative anabolic strategies that can enhance anabolic, osteogenic potential are actively sought. Sex steroid hormones, particularly estrogens, are bidirectional regulators for bone homeostasis; therefore, estrogen-mediated events are important potential targets for such anabolic therapies. Here, we show that estrogen-induced, osteoanabolic effects were mediated via enhanced production of chondroitin sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based system. Conversely, estrogen deficiency caused reduced expression of CS-E-synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E production in cultures of bone marrow cells derived from ovariectomized mice. Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted from impaired osteoblast differentiation. These results indicated that strategies aimed at boosting CS-E biosynthesis are promising alternative therapies for osteoporosis.
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spelling pubmed-43557302015-03-17 Chondroitin sulfate-E mediates estrogen-induced osteoanabolism Koike, Toshiyasu Mikami, Tadahisa Shida, Miharu Habuchi, Osami Kitagawa, Hiroshi Sci Rep Article Osteoporosis is an age-related disorder of bone remodeling in which bone resorption outstrips bone matrix deposition. Although anticatabolic agents are frequently used as first-line therapies for osteoporosis, alternative anabolic strategies that can enhance anabolic, osteogenic potential are actively sought. Sex steroid hormones, particularly estrogens, are bidirectional regulators for bone homeostasis; therefore, estrogen-mediated events are important potential targets for such anabolic therapies. Here, we show that estrogen-induced, osteoanabolic effects were mediated via enhanced production of chondroitin sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based system. Conversely, estrogen deficiency caused reduced expression of CS-E-synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E production in cultures of bone marrow cells derived from ovariectomized mice. Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted from impaired osteoblast differentiation. These results indicated that strategies aimed at boosting CS-E biosynthesis are promising alternative therapies for osteoporosis. Nature Publishing Group 2015-03-11 /pmc/articles/PMC4355730/ /pubmed/25759206 http://dx.doi.org/10.1038/srep08994 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Koike, Toshiyasu
Mikami, Tadahisa
Shida, Miharu
Habuchi, Osami
Kitagawa, Hiroshi
Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
title Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
title_full Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
title_fullStr Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
title_full_unstemmed Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
title_short Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
title_sort chondroitin sulfate-e mediates estrogen-induced osteoanabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355730/
https://www.ncbi.nlm.nih.gov/pubmed/25759206
http://dx.doi.org/10.1038/srep08994
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