The microRNA-455 null mouse shows dysregulated bone turnover

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.