MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) have been identified in many adult tissues and they have been closely studied in recent years, especially in view of their potential use for treating diseases and damaged tissues and organs. MSCs are capable of self-replication and differentiation into osteoblasts and are considered an important source of cells in tissue engineering for bone regeneration. Several epigenetic factors are believed to play a role in the osteogenic differentiation of MSCs, including microRNAs (miRNAs). MiRNAs are small, single-stranded, non-coding RNAs of approximately 22 nucleotides that are able to regulate cell proliferation, differentiation and apoptosis by binding the 3′ untranslated region (3′-UTR) of target mRNAs, which can be subsequently degraded or translationally silenced. MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1(Wnt)/β-catenin signaling pathways. This review provides an overview of the miRNAs involved in osteogenic differentiation and how these miRNAs could regulate the expression of target genes.

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

“…MicroRNAs (miRNAs) are endogenous 22-nucleotide long non-coding RNAs that regulate gene expression by binding to the 3´ untranslated region (UTR) of their target mRNAs and promoting mRNA degradation and/or inhibiting RNA translation. MiRNAs have been shown to play an important role in the osteogenic lineage commitment of MSCs by targeting the expression of transcription factors and components of the primary bone formation pathways [ 40 ]. Important differences in the expression of specific miRNAs have been found for HD-MSCs and MM-MSCs when subjected to osteogenic differentiation conditions.…”

Bioinformatics Analysis Identified miR-584-5p and Key miRNA-mRNA Networks Involved in the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

“…It has been reported that miRNA can regulate the osteogenic differentiation of BMSCs and PDLSCs. For BMSC, MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1(Wnt)/β- catenin signaling pathways ( Mazziotta et al, 2021 ). In previous literature, miR-17, miR-21, miR23a, miR-24, miR-132, miR-138, miR-214, miR-218, miR-543, and miR1305 have been reported to regulate PDLSCs Osteogenic differentiation ( Ahmad et al, 2021 ).…”

microRNAs in the Regulation of Melanogenesis

“…It is now estimated that miRNAs target approximately 60% of genes in humans and other mammals [ 42 ]. Due to their role in mRNA expression regulation, miRNAs are involved in all cellular activities, including proliferation, differentiation, migration, apoptosis, and immune responses, both in normal and pathological conditions [ 43 , 44 , 45 , 46 ]. Several mechanisms ensure high stability in miRNAs.…”

“…miRNA activity mainly induces gene expression reduction by binding to sequences in the 3′ untranslated region (3′-UTR) of target genes. This can lead to mRNA target degradation, or inhibition of translation and reduction in protein levels [ 45 ]. However, miRNA activities show higher complexity as each miRNA can target different genes and several miRNAs can regulate the same gene’s expression.…”

“…However, miRNA activities show higher complexity as each miRNA can target different genes and several miRNAs can regulate the same gene’s expression. Moreover, the strict interplay between long non-coding RNAs (lncRNAs) and miRNAs contributes to gene expression regulation [ 40 , 45 , 49 ].…”