Niu, L., Swingler, T.E., Suelzu, C. et al. (7 more authors) (2025) The microRNA-455 null mouse shows dysregulated bone turnover. JBMR Plus, 9 (3). ISSN 2473-4039
Abstract
A wide range of specific microRNAs have been shown to have either positive or negative effects on osteoblast differentiation and function, with consequent changes in postnatal bone mass. A number of specific targets have been identified. We previously used CrispR-Cas9 to make a miR-455 null mouse, characterizing a behavioral phenotype with age. The current study identifies a bone phenotype, starting in younger animals. At 3 weeks of age, the miR-455 null mice (both male and female) display increased length of both long bones and vertebrae and, while this difference diminishes across 1 year, it remains significant. Increased bone formation in vivo is mirrored by an increase in osteogenesis from bone marrow–derived stem cells in vitro. This is accompanied by a decrease in osteoclastogenesis and osteoclast function. MicroCT analyses show increased trabecular bone and less porosity/decreased separation in the miR-455 null mouse, suggesting a more dense and stronger bone at 3 weeks of age; these differences normalize by 1 year. Gain-of-function and loss-of-function datasets show that FGF18 expression is regulated by miR-455 and FGF18 was validated as a direct target of miR-455. The regulation of FGF18 by miR-455 is a likely mediator of its effect on bone.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | microRNA; miR-455; null mouse; bone; FGF18 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Mar 2025 15:57 |
Last Modified: | 04 Mar 2025 15:57 |
Status: | Published |
Publisher: | Oxford University Press (OUP) |
Refereed: | Yes |
Identification Number: | 10.1093/jbmrpl/ziaf007 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223938 |