Osteoclast-derived extracellular miR-106a-5p promotes osteogenic differentiation and facilitates bone defect healing

Abstract

Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling, osteoclasts generate large amounts of sEVs. However, there is very few research studying whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p as highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro. Next, we prepared an sEV-modified demineralized bone matrix (DBM) as scaffold treating calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo results indicated that DBM modified with miR-106a-5p-sEVs showed an enhanced capacity for bone regeneration. This important finding further emphasizes that sEV-mediated miR-106a-5p transfer plays a critical role in osteogenesis and indicates a novel communication mode between osteoclasts and BMSCs.

Keywords: Bone remodeling; Intercellular communication; Osteogenic differentiation; Small extracellular vesicles; miRNA.