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The microRNA-455 null mouse shows dysregulated bone turnover

Lookup NU author(s): Dr Matthew BarterORCiD, Dan Hayman, Professor David YoungORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s).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.

Publication metadata

Author(s): Niu L, Swingler TE, Suelzu C, Ersek A, Orriss IR, Barter MJ, Hayman DJ, Young DA, Horwood N, Clark IM

Publication type: Article

Publication status: Published

Journal: JBMR Plus

Year: 2025

Volume: 9

Issue: 3

Print publication date: 01/03/2025

Online publication date: 12/01/2025

Acceptance date: 09/01/2025

Date deposited: 03/03/2025

ISSN (electronic): 2473-4039

Publisher: Oxford University Press

URL: https://doi.org/10.1093/jbmrpl/ziaf007

DOI: 10.1093/jbmrpl/ziaf007

Data Access Statement: RNASeq data are available via the Gene Expression Omnibus (https:// www.ncbi.nlm.nih.gov/geo/).

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