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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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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965124/
https://www.ncbi.nlm.nih.gov/pubmed/31949279
http://dx.doi.org/10.1038/s42003-020-0754-2
Descripción
Sumario: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.