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

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

Communications Biology

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.

eng

Nature Research

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[ISSN] 2399-3642

[DOI] 10.1038/s42003-020-0754-2

[PMID] 31949279

[DOI] https://doi.org/10.1038/s42003-020-0754-2