The microRNA-455 null mouse shows dysregulated bone turnover

Niu, Lingzi, Swingler, Tracey E., Suelzu, Caterina, Ersek, Adel, Orriss, Isabel R., Barter, Matthew J., Hayman, Dan J., Young, David A., Horwood, Nicole and Clark, Ian M. (2025) The microRNA-455 null mouse shows dysregulated bone turnover. Journal of Bone and Mineral Research Plus. ISSN 2473-4039

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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 post-natal bone mass; a number of specific targets have been identified. We previously used CrispR-Cas9 to make a miR-455 null mouse, characterising a behavioural phenotype with age. The current study identifies a bone phenotype, starting in younger animals. At three weeks of age, the miR-455 null mice (both male and female) display increased length of both long bones and vertebrae and whilst 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 three weeks of age, these differences normalise by 1 year. Gain-of-function and loss-of-function datasets shows 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.

Item Type:	Article
Uncontrolled Keywords:	3* ,/dk/atira/pure/researchoutput/REFrank/3_
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	LivePure Connector
Date Deposited:	10 Jan 2025 01:01
Last Modified:	11 Feb 2025 01:25
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98146
DOI:	10.1093/jbmrpl/ziaf007

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