Cell penetrating peptide mediated delivery of has-miRNA-29b to promote mesenchymal stem cell differentiation into osteogenic lineage

J.S. Suh, J.Y. Lee, Y.S. Choi, C.P. Chung, Y.J. Park
Seoul National University, KR

Keywords: MicroRNA-29b, cell-penetrating peptide, human mesenchymal stem cells, non-toxic intracellular transfection, osteogenic differentiation

Summary:

MicroRNAs regulate biological processes by binding to mRNA 3’-untranslated region (UTR) sequences to attenuate protein synthesis. We used that miRNA-29b supports osteoblast differentiation through several mechanisms. The miRNA-29b is a key regulator of development of the osteoblast phenotype by targeting anti-osteogenic factors and modulating bone extracellular matrix proteins. However, the main limiting factor in the use of miRNAs is their reduced penetration into cells. Recently, several cell-penetrating peptides (CPPs) have been investigated as a means to overcome the limited penetration of oligonucleotides such as miRNAs. Herein, the arginine-rich CPP, called the low-molecular weight protamine (LMWP), is the sequence from natural protamine. We worked out the difficult problem to transfect into hMSCs by the complex with LMWP, and then we investigated synthetic double-stranded miR-29b could be induced osteoblast differentiation. Taken together, it is significant that we would believe our results that is to open the high efficient application of miRNAs as therapeutic drug and revalidates the efficacy of miR-29b in bone regeneration field. Furthermore, this therapeutic strategy may be applicable to bone regeneration in local treatment and deserves further investigation in vivo.