The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice

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 bone-forming osteoblasts and have a well-established role in initiation of bone mineralization, in osteoclastogenesis. We show that the...

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Bibliographic Details
Published in:	Communications biology Vol. 3; no. 1; p. 30
Main Authors:	Minamizaki, Tomoko, Nakao, Yuko, Irie, Yasumasa, Ahmed, Faisal, Itoh, Shota, Sarmin, Nushrat, Yoshioka, Hirotaka, Nobukiyo, Asako, Fujimoto, Chise, Niida, Shumpei, Sotomaru, Yusuke, Tanimoto, Kotaro, Kozai, Katsuyuki, Sugiyama, Toshie, Bonnelye, Edith, Takei, Yuichiro, Yoshiko, Yuji
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 16-01-2020 Nature Publishing Group
Subjects:	13/1 13/109 13/31 13/51 14/28 38/61 38/77 631/337/384/331 631/80/86/820 64/60 Animal models Animals Biological Transport Biology Biomarkers Biomedical and Life Sciences Bone growth Bone loss Bone mass Bone matrix Bone Matrix - metabolism Bone resorption Bone Resorption - genetics Bone Resorption - metabolism Bone Resorption - pathology Bone turnover Cancellous bone Cancer Cell Communication Extracellular Vesicles - metabolism Gene Expression Regulation Glial stem cells Immunohistochemistry Life Sciences Matrix vesicles Mice Mice, Transgenic MicroRNAs - genetics Mineralization Osteoblasts Osteoblasts - metabolism Osteoclastogenesis Osteoclasts Osteoclasts - metabolism Osteogenesis Osteogenesis - genetics Osteoprogenitor cells Positive Regulatory Domain I-Binding Factor 1 - genetics RNA Interference Signal Transduction Transcription Transgenic mice Vitamin D
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Summary:	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 bone-forming 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. Minamizaki et al. show that osteoblast-specific overexpression of miR-125b , a cargo of matrix vesicles, increases the bone mass from a reduced number of osteoclasts in mice. This study suggests that bone matrix stores miR-125b which inhibits bone resorption by downregulating PRDM1, a transcriptional repressor of anti-osteoclastogenic factors.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2399-3642 2399-3642
DOI:	10.1038/s42003-020-0754-2