MicroRNAs Regulation in Osteogenic Differentiation of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cell with the potential of self-renewal and multidirectional differentiation. They can be obtained from a variety of tissues and can differentiate into a variety of cell types under different induction conditions, including osteoblasts. Because of this osteogenic property, MSCs have attracted much attention in the treatment of bone metabolism-related diseases. MicroRNAs (miRNAs), as an epigenetic factor, are thought to play an important regulatory role in the process of osteogenic differentiation of MSCs. In recent years, increasingly evidence shows that miRNAs imbalance is involved in the regulation of osteoporosis and fracture. In this review, miRNAs involved in osteogenic differentiation and their mechanisms for regulating the expression of target genes are reviewed. In addition, we also discuss the potential clinical applications and possible directions of this field in the future.

Unravelling microRNA regulation and miRNA–mRNA regulatory networks in osteogenesis driven by 3D nanotopographical cues

“…They control the expression of genes through various mechanisms such as direct repression of translation via complementary binding, feedback and feedforward loops and competition with shared miRNAs and shared regulation. 73,74 miRNA control in the biochemically guided differentiation of MSCs into osteogenic lineage is known; [75][76][77] however, the miRNA regulation in the matrixguided differentiation of MSCs into osteogenic lineage is unknown, and the comparison of miRNA regulation under biochemical versus matrix cues have not been attempted.…”

Role of microRNAs in osteogenesis of stem cells

“…The use of exogenous miRNA regulation tools such as miRNA over‐expressing vectors, miRNA mimics, miRNA antisense oligonucleotides or antagomiRs (chemically modified RNA oligonucleotides that are complementary with target miRNAs), miRNA‐sponge or miRNA‐decoys (contains multiple tandem binding sites for interacting with corresponding miRNA and serves as a competitive inhibitor of miRNA:mRNA binding) and miRNA‐mask (oligonucleotides complementary to 3′‐UTR of target mRNAs to block miRNA‐mRNA interaction) may provide important clues for development of new therapeutics for bone defects and fracture. For example, overexpression of anti‐miR‐34, anti‐miR‐100, and anti‐miR‐140‐5p is considered for bone regeneration promotion …”

“…Overexpression of miR-144-3p inhibits osteogenic differentiation of C3H10T1/2 cells by targeting Smad4. 115,154 miR-155 expression is downregulated in MC3T3-E1 cells during BMP2-induced osteogenic differentiation. MiR-155 exerts its antiosteogenic effect by suppressing Smad5.…”

“…miR‐144‐3p is down‐regulated during osteoblast differentiation. Overexpression of miR‐144‐3p inhibits osteogenic differentiation of C3H10T1/2 cells by targeting Smad4 . miR‐155 expression is downregulated in MC3T3‐E1 cells during BMP2‐induced osteogenic differentiation.…”

“…For example, overexpression of anti-miR-34, anti-miR-100, and anti-miR-140-5p is considered for bone regeneration promotion. 115 Overall, miRNAs have emerged as novel powerful and dynamic modifiers of bone regeneration. Tremendous progress has been made to understand the relationship between miRNAs specific mechanism and osteogenesis and many evidence demonstrating the ability of miRNA mimics or miRNA inhibitors in modulation of osteogenesis, bone formation processes and improvement of bone diseases.…”