<p>Effects of miR-26a on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by a Mesoporous Silica Nanoparticle - PEI - Peptide System</p>

Abstract

Introduction: RNA-based therapy for bone repair and regeneration is a highly safe and effective approach, which has been extensively investigated in recent years. However, the molecular stability of RNA agents still remains insufficient for clinical application. High porosity, tunable size, and ideal biodegradability and biosafety are a few of the characters of mesoporous silicon nanoparticles (MSNs) that render them a promising biomaterial carrier for RNA treatment. Materials and Methods: In this study, a novel miR-26a delivery system was constructed based on MSNs. Next, we assessed the miRNA protection of the delivery vehicles. Then, rat bone marrow mesenchymal stem cells (rBMSCs) were incubated with the vectors, and the transfection efficiency, cellular uptake, and effects on cell viability and osteogenic differentiation were evaluated. Results: The results demonstrated that the vectors protected miR-26a from degradation in vitro and delivered it into the cytoplasm. A relatively low concentration of the delivery systems significantly increased osteogenic differentiation of rBMSCs. Conclusion: The vectors constructed in our study provide new methods and strategies for the delivery of microRNAs in bone tissue engineering.

FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy

“…FOXO3 gene was first amplified from template plasmid pcDNA3 FLAG-human FOXO3 (Addgene, Watertown, MA, USA) using polymerase chain reaction (PCR). Then, the product of PCR was cloned into the pENTR11 vector (A10467, Invitrogen, USA) and recombined with Gateway LR Clonase II enzyme mix (11,791,020; Invitrogen, USA) in the Gateway lentiviral expression plasmid pLenti CMV Puro DEST (w118-1) (17,452; Addgene, USA). Small interfering RNA for FOXO3 (siFOXO3; catalog number: A09003) was synthesized by Gene Pharma (Shanghai, China).…”

“…The previous studies showed that Forkhead Box O3 (FOXO3) plays a critical role in osteogenic differentiation through inducing autophagy [6], and that FOXO3 might be the target of miR-96-5p, miR-629 and miR-149 [7][8][9]. MiRNAs, which are a class of endogenous RNAs of 19-25 nucleotides in total length, exert post-transcriptional effects on gene expressions, and some of them have been also found to affect osteogenic differentiation of MSCs [10,11]. The previous study showed that FOXO3 was the target for miR-223-3p [12].…”

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration—A Review

“…In the repair of rat femoral defects, Yuan et al [ 117 ] seeded anti-miRNA-26a-5p-modified adipose-derived mesenchymal stem cells (ADSCs) on biphasic calcium phosphate (BCP) scaffolds, which resulted in an accelerated bone formation via the Wnt/Ca 2+ signaling pathway. This is indeed a very interesting finding, since Yan et al [ 115 ] reported an osteogenic differentiation of rat bone marrow stem cells due to miRNA-26a encapsulated into silica mesopores and Zhang et al [ 104 ] reported on the activation of osteoblastic activity of endogenous stem cells as a result from miRNA-26a loaded into cell-free 3D-printed scaffolds. The discrepancy in findings between the results reported by Yuan et al [ 117 ] and the other two studies might be due to the use of ADSCs in the former.…”

“…Silica has been used for miRNA delivery as well for bone regeneration purposes, especially mesoporous silica nanoparticles, which are ideal for drug delivery and are promising in gene transfection [ 114 ]. Recently, Yan et al [ 115 ] encapsulated miRNA-26a mimics into silica mesopores that were coated with PEI. The surface was then conjugated with peptides.…”

“…The surface was then conjugated with peptides. This system protected miRNA from degradation and resulted in an increased osteogenic differentiation of rat bone marrow MSCs, even at relatively low concentrations [ 115 ].…”