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