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

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The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice.
Communications Biology ( IF 5.2 ) Pub Date : 2020-01-16 , DOI: 10.1038/s42003-020-0754-2
Tomoko Minamizaki ₁ , Yuko Nakao _{1,

2} , Yasumasa Irie _{1,

3} , Faisal Ahmed ₁ , Shota Itoh _{1,

2} , Nushrat Sarmin ₁ , Hirotaka Yoshioka _{1,

4} , Asako Nobukiyo ₅ , Chise Fujimoto ₁ , Shumpei Niida ₆ , Yusuke Sotomaru ₅ , Kotaro Tanimoto ₂ , Katsuyuki Kozai ₃ , Toshie Sugiyama ₇ , Edith Bonnelye ₈ , Yuichiro Takei _{1,

9} , Yuji Yoshiko ₁

Affiliation

Department of Calcified Tissue Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Department of Anatomy, School of Medicine, International University of Health and Welfare, 4-3 Kozunomori, Narita, 286-8686, Japan.
Natural Science Center of Basic Research and Development, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, 474-8551, Japan.
Department of Animal Science, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-ku, Niigata, 950-2181, Japan.
CNRS ERL 6001/ INSERM U1232, Institut de Cancérologie de l'Quest, 44805, Saint-Herblain, France.
Department of Nutrition, Faculty of Nutrition, University of Kochi, 2751-1 Ike, Kochi, 781-8515, Japan.

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.

中文翻译：

基质小泡货物miR-125b积聚在骨基质中，抑制了小鼠的骨吸收。

成骨细胞和破骨细胞之间的通讯在骨代谢中起关键作用。我们在这里描述了基质囊泡（MVs）的意外作用，它从成骨性成骨细胞中萌芽，并在破骨细胞形成过程中在骨矿化的起始中具有公认的作用。我们显示，MV货物miR-125b累积在骨基质中，在成骨细胞中过表达miR-125b的转基因（Tg）小鼠中累积增加。Tg小鼠的骨形成和成骨细胞正常，但是吸收骨的破骨细胞数量减少，导致小梁骨量增加。骨基质中的miR-125b靶向并降解破骨细胞前体中抗破骨细胞形成因子的转录阻遏物Prdm1。在不同小鼠模型中，成骨细胞中过表达的miR-125b消除了骨质流失。

更新日期：2020-01-16

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