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ID 48981
file
creator
Nakao, Yuko
Irie, Yasumasa
Ahmed, Faisal
Itoh, Shota
Sarmin, Nushrat
Fujimoto, Chise
Niida, Shumpei
Sugiyama, Toshie
Bonnelye, Edith
abstract
Communication between osteoblasts and osteoclasts plays a key role in bone metabolism. We describe here an unexpected role for matrix vesicles (MVs), which bud from boneforming osteoblasts and have a well-established role in initiation of bone mineralization, in osteoclastogenesis. We show that the MV cargo miR-125b accumulates in the bone matrix, with increased accumulation in transgenic (Tg) mice overexpressing miR-125b in osteoblasts. Bone formation and osteoblasts in Tg mice are normal, but the number of bone-resorbing osteoclasts is reduced, leading to higher trabecular bone mass. miR-125b in the bone matrix targets and degrades Prdm1, a transcriptional repressor of anti-osteoclastogenic factors, in osteoclast precursors. Overexpressing miR-125b in osteoblasts abrogates bone loss in different mouse models. Our results show that the MV cargo miR-125b is a regulatory element of osteoblast-osteoclast communication, and that bone matrix provides extracellular storage of miR-125b that is functionally active in bone resorption.
description
T.M. and Y.T. were supported in part by MEXT KAKENHI (JP16K11443, T.M.; JP26861548, Y.T.). Y.Y. was supported by MEXT KAKENHI (JP18K19647), the Raffinee International Foundation and the Ono Pharmaceutical Foundation.
Supplementary information is available for this paper at https://doi.org/10.1038/s42003-020-0754-2.
journal title
Communications Biology
volume
Volume 3
start page
30
date of issued
2020-01-16
publisher
Nature Research
issn
2399-3642
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
publisher
rights
© The Author(s) 2020. 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/.
relation url
department
Graduate School of Biomedical & Health Sciences
Graduate School of Biomedical & Health Sciences
Natural Science Center for Basic Research and Development