Promotion of the immunomodulatory properties and osteogenic differentiation of adipose-derived mesenchymal stem cells in vitro by lentivirus-mediated mir-146a sponge expression.

Mesenchymal stem cells (MSCs) exert beneficial effects on the repair of bone tissue via both immunomodulatory functions and osteogenic differentiation. As one of the first miRNAs identified that regulate innate immune responses, miR-146a has been reported to serve as a negative-feedback regulator in several chronic inflammatory diseases. However, the majority of studies focus on understanding how miRNA-146a regulates immune cells and the associated immune-based disorders. In the present study, we employed miRNA sponges that were forcibly expressed using a lentiviral vector to knock down the expression of miR-146a in human adipose-derived stem cells (hASCs). The hASCs transduced with miR-146a sponges exhibited enhanced immunomodulatory properties, as evidenced by the increased production of key immunosuppressive factors. These factors were able to elevated expression of anti-inflammatory genes and inhibited the expression of inflammatory genes in macrophages. Further mechanistic studies showed that the suppression of miR-146a activated NF-κB signaling in hASCs, suggesting its regulatory role in miR-146a sponge-induced immunomodulatory changes in hASCs. In addition, the suppression of miR-146a was also found to stimulate the osteogenic differentiation of hASCs. The observed upregulation of SMAD4 expression indicated the involvement of SMAD4 in modulating the osteogenic potential of hASCs in response to miR-146a suppression. Our study contributes to the understanding of the effects of miR-146a on the immunomodulatory properties and osteogenic differentiation of hASCs and highlights the potential use of miRNA-146a sponges modified hASCs as seed cells for bone tissue engineering.