MicroRNA-5106-based nanodelivery to enhance osteogenic differentiation and bone regeneration of bone mesenchymal stem cells through targeting of Gsk-3 alpha

Regulating bone mesenchymal stem cell (BMSC) differentiation into osteoblastic lineage plays a significant role in bone tissue regeneration. MicroRNAs are highly conserved small noncoding RNAs that mediate some special cell behaviors through repressing or upregulating the mRNA expression of their target genes. Here, we show that microRNA-5106 (miR-5106) modulates and enhances the osteoblastic differentiation of BMSCs through liposome-based delivery and transfection. The results revealed that miR-5106 was up-regulated during the differentiation of BMSCs. The overexpression of miR-5106 significantly promoted the alkaline phosphatase (ALP) activity, expressions of osteoblast-specific genes and extracellular matrix mineralization, whereas the inhibition of miR-5106 functioned by anti-miR-5106 (miR-5106 inhibitor) significantly decreased the osteoblastic differentiation of BMSCs. Further studies indicated that miR-5106 enhances the osteogenic differentiation of BMSCs through inhibiting Gsk-3 alpha in the Wnt/beta-catenin pathway. The delivery of the miR-5106 complex significantly enhanced the critical-sized bone defect healing in vivo. We anticipate that our findings could provide a new miRNA-based therapeutic method and an osteoblastic molecular mechanism for enhancing bone tissue regeneration.