Dataset Information

Osteoblast-targeted delivery of miR-33-5p attenuates osteopenia development induced by mechanical unloading in mice.

ABSTRACT: A growing body of evidence has revealed that microRNAs (miRNAs) play crucial roles in regulating osteoblasts and bone metabolism. However, the effects of miRNAs in osteoblast mechanotransduction remain to be defined. In this study, we investigated the regulatory effect of miR-33-5p in osteoblasts and tested its anti-osteopenia effect when delivered by an osteoblast-targeting delivery system in vivo. First, we demonstrated that miR-33-5p could promote the activity and mineralization of osteoblasts without influencing their proliferation in vitro. Then our data showed that supplementing miR-33-5p in osteoblasts by a targeted delivery system partially recovered the osteopenia induced by mechanical unloading at the biochemical, microstructural, and biomechanical levels. In summary, our findings demonstrate that miR-33-5p is a key factor in the occurrence and development of the osteopenia induced by mechanical unloading. In addition, targeted delivery of the mimics of miR-33-5p is a promising new strategy for the treatment of pathological osteopenia.

SUBMITTER: Wang H

PROVIDER: S-EPMC5833703 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Osteoblast-targeted delivery of miR-33-5p attenuates osteopenia development induced by mechanical unloading in mice.

Wang Han H Hu Zebing Z Shi Fei F Dong Jingjing J Dang Lei L Wang Yixuan Y Sun Zhongyang Z Zhou Hua H Zhang Shu S Cao Xinsheng X Zhang Ge G

Cell death & disease 20180207 2

A growing body of evidence has revealed that microRNAs (miRNAs) play crucial roles in regulating osteoblasts and bone metabolism. However, the effects of miRNAs in osteoblast mechanotransduction remain to be defined. In this study, we investigated the regulatory effect of miR-33-5p in osteoblasts and tested its anti-osteopenia effect when delivered by an osteoblast-targeting delivery system in vivo. First, we demonstrated that miR-33-5p could promote the activity and mineralization of osteoblast ...[more]

PMID: 29415986

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Project description:Developing novel approaches to treat skeletal disorders requires an understanding of how critical molecular factors regulate osteoblast differentiation and bone remodeling. We have reported that (1) retinoic acid receptor-related orphan receptor beta (Ror?) is upregulated in bone samples isolated from aged mice and humans in vivo; (2) Ror? expression is inhibited during osteoblastic differentiation in vitro; and (3) genetic deletion of Ror? in mice results in preservation of bone mass during aging. These data establish that Ror? inhibits osteogenesis and that strict control of Ror? expression is essential for bone homeostasis. Because microRNAs (miRNAs) are known to play important roles in the regulation of gene expression in bone, we explored whether a predicted subset of nine miRNAs regulates Ror? expression during both osteoblast differentiation and aging. Mouse osteoblastic cells were differentiated in vitro and assayed for Ror? and miRNA expression. As Ror? levels declined with differentiation, the expression of many of these miRNAs, including miR-219a-5p, was increased. We further demonstrated that miR-219a-5p was decreased in bone samples from old (24-month) mice, as compared with young (6-month) mice, concomitant with increased Ror? expression. Importantly, we also found that miR-219a-5p expression was decreased in aged human bone biopsies compared with young controls, demonstrating that this phenomenon also occurs in aging bone in humans. Inhibition of miR-219a-5p in mouse calvarial osteoblasts led to increased Ror? expression and decreased alkaline phosphatase expression and activity, whereas a miR-219a-5p mimic decreased Ror? expression and increased osteogenic activity. Finally, we demonstrated that miR-219a-5p physically interacts with Ror? mRNA in osteoblasts, defining Ror? as a true molecular target of miR-219a-5p. Overall, our findings demonstrate that miR-219a-5p is involved in the regulation of Ror? in both mouse and human bone. © 2018 American Society for Bone and Mineral Research.

Dataset Information

Osteoblast-targeted delivery of miR-33-5p attenuates osteopenia development induced by mechanical unloading in mice.

Publications

Osteoblast-targeted delivery of miR-33-5p attenuates osteopenia development induced by mechanical unloading in mice.

Similar Datasets

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