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Regulation of bone metabolism by megakaryocytes in a paracrine manner

Megakaryocytes (MKs) play key roles in regulating bone metabolism. To test the roles of MK-secreted factors, we investigated whether MK and promegakaryocyte (pro-MK) conditioned media (CM) may affect bone formation and resorption. K562 cell lines were differentiated into mature MKs. Mouse bone marro...

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Autores principales: Lee, Young-Sun, Kwak, Mi Kyung, Moon, Sung-Ah, Choi, Young Jin, Baek, Ji Eun, Park, Suk Young, Kim, Beom-Jun, Lee, Seung Hun, Koh, Jung-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010738/
https://www.ncbi.nlm.nih.gov/pubmed/32042021
http://dx.doi.org/10.1038/s41598-020-59250-6
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author Lee, Young-Sun
Kwak, Mi Kyung
Moon, Sung-Ah
Choi, Young Jin
Baek, Ji Eun
Park, Suk Young
Kim, Beom-Jun
Lee, Seung Hun
Koh, Jung-Min
author_facet Lee, Young-Sun
Kwak, Mi Kyung
Moon, Sung-Ah
Choi, Young Jin
Baek, Ji Eun
Park, Suk Young
Kim, Beom-Jun
Lee, Seung Hun
Koh, Jung-Min
author_sort Lee, Young-Sun
collection PubMed
description Megakaryocytes (MKs) play key roles in regulating bone metabolism. To test the roles of MK-secreted factors, we investigated whether MK and promegakaryocyte (pro-MK) conditioned media (CM) may affect bone formation and resorption. K562 cell lines were differentiated into mature MKs. Mouse bone marrow macrophages were differentiated into mature osteoclasts, and MC3T3-E1 cells were used for osteoblastic experiments. Bone formation was determined by a calvaria bone formation assay in vivo. Micro-CT analyses were performed in the femurs of ovariectomized female C57B/L6 and Balb/c nude mice after intravenous injections of MK or pro-MK CM. MK CM significantly reduced in vitro bone resorption, largely due to suppressed osteoclastic resorption activity. Compared with pro-MK CM, MK CM suppressed osteoblastic differentiation, but stimulated its proliferation, resulting in stimulation of calvaria bone formation. In ovariectomized mice, treatment with MK CM for 4 weeks significantly increased trabecular bone mass parameters, such as bone volume fraction and trabecular thickness, in nude mice, but not in C57B/L6 mice. In conclusion, MKs may secrete anti-resorptive and anabolic factors that affect bone tissue, providing a novel insight linking MKs and bone cells in a paracrine manner. New therapeutic agents against metabolic bone diseases may be developed from MK-secreted factors.
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spelling pubmed-70107382020-02-21 Regulation of bone metabolism by megakaryocytes in a paracrine manner Lee, Young-Sun Kwak, Mi Kyung Moon, Sung-Ah Choi, Young Jin Baek, Ji Eun Park, Suk Young Kim, Beom-Jun Lee, Seung Hun Koh, Jung-Min Sci Rep Article Megakaryocytes (MKs) play key roles in regulating bone metabolism. To test the roles of MK-secreted factors, we investigated whether MK and promegakaryocyte (pro-MK) conditioned media (CM) may affect bone formation and resorption. K562 cell lines were differentiated into mature MKs. Mouse bone marrow macrophages were differentiated into mature osteoclasts, and MC3T3-E1 cells were used for osteoblastic experiments. Bone formation was determined by a calvaria bone formation assay in vivo. Micro-CT analyses were performed in the femurs of ovariectomized female C57B/L6 and Balb/c nude mice after intravenous injections of MK or pro-MK CM. MK CM significantly reduced in vitro bone resorption, largely due to suppressed osteoclastic resorption activity. Compared with pro-MK CM, MK CM suppressed osteoblastic differentiation, but stimulated its proliferation, resulting in stimulation of calvaria bone formation. In ovariectomized mice, treatment with MK CM for 4 weeks significantly increased trabecular bone mass parameters, such as bone volume fraction and trabecular thickness, in nude mice, but not in C57B/L6 mice. In conclusion, MKs may secrete anti-resorptive and anabolic factors that affect bone tissue, providing a novel insight linking MKs and bone cells in a paracrine manner. New therapeutic agents against metabolic bone diseases may be developed from MK-secreted factors. Nature Publishing Group UK 2020-02-10 /pmc/articles/PMC7010738/ /pubmed/32042021 http://dx.doi.org/10.1038/s41598-020-59250-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lee, Young-Sun
Kwak, Mi Kyung
Moon, Sung-Ah
Choi, Young Jin
Baek, Ji Eun
Park, Suk Young
Kim, Beom-Jun
Lee, Seung Hun
Koh, Jung-Min
Regulation of bone metabolism by megakaryocytes in a paracrine manner
title Regulation of bone metabolism by megakaryocytes in a paracrine manner
title_full Regulation of bone metabolism by megakaryocytes in a paracrine manner
title_fullStr Regulation of bone metabolism by megakaryocytes in a paracrine manner
title_full_unstemmed Regulation of bone metabolism by megakaryocytes in a paracrine manner
title_short Regulation of bone metabolism by megakaryocytes in a paracrine manner
title_sort regulation of bone metabolism by megakaryocytes in a paracrine manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010738/
https://www.ncbi.nlm.nih.gov/pubmed/32042021
http://dx.doi.org/10.1038/s41598-020-59250-6
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