MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling

- The role of miR-467g is not known in the regulation of osteoblast functions.
- MiR-467g inhibits osteoblast functions and directly targets Runx-2 and Hhip genes to regulate osteogenesis.
- MiR-467g inhibits new bone regeneration by negatively regulating Ihh/Runx-2 signaling pathway.
- Therapeutic approaches targeting miR-467g could be useful in enhancing the new bone formation and treatment of pathological conditions of bone loss.

MicroRNAs are important post transcriptional regulators of gene expression and play critical role in osteoblast differentiation. In this study we report miR-467g, an uncharacterized novel miRNA, in regulation of osteoblast functions. Over-expression of miR-467g inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3′ UTR reporter assay identified Runx-2 as a direct target of miR-467g. Over expression of miR-467g in osteoblasts down regulated Runx-2 and Ihh signaling components. Furthermore, silencing of miR-467g was done to see its role in Ihh and Runx-2 mediated bone healing and regeneration in a drill hole injury model in BALB/c mice. Silencing of miR-467g led to significant increase in new bone regeneration and Ihh and Runx-2 localization at injury site in a day dependent manner. In conclusion, miR-467g negatively regulates osteogenesis by targeting Ihh/Runx-2 signaling. We, thus, propose that therapeutic approaches targeting miR-467g could be useful in enhancing the new bone formation.