FIGURE 4.

MicroRNAs (miRNAs) in fracture non‐union. Mechanism of action of miR‐31‐5p, miR‐221 and miR‐451‐5p involved in non‐union fractures. ‘+’ indicates promotion, while ‘–’ indicates inhibition of the target gene or pathway. This regulation does not necessarily represent the direct target of the miRNA but rather the overall downstream pathway regulation. Main effect of miR‐31‐5p is the reduction of osteogenesis by inhibition of runt‐related transcription factor 2 (RUNX2) and bone morphogenic protein 2 (BMP2) expression. miR‐221 leads to increased fibroblast proliferation by upregulation of platelet‐derived growth factor (PDGFA). miR‐451‐5p in general decreases cell growth, migration and angiogenesis, all critical factors for fracture healing.