MicroRNAs regulate signaling pathways in osteogenic differentiation of mesenchymal stem cells (Review)

Abstract

Osteogenesis is a complex multi-step process involving the differentiation of mesenchymal stem cells (MSCs) into osteoblast progenitor cells, preosteoblasts, osteoblasts and osteocytes, and the crosstalk between multiple cell types for the formation and remodeling of bone. The signaling regulatory networks during osteogenesis include various components, including growth factors, transcription factors, micro (mi)RNAs and effectors, a number of which form feedback loops controlling the balance of osteogenic differentiation by positive or negative regulation. miRNAs have been found to be important regulators of osteogenic signaling pathways in multiple aspects and multiple signaling pathways. The present review focusses on the progress in elucidating the role of miRNA in the osteogenesis signaling networks of MSCs as a substitute for bone implantation the the field of bone tissue engineering. In particular, the review classifies which miRNAs promote or suppress the osteogenic process, and summarizes which signaling pathway these miRNAs are involved in. Improvements in knowledge of the characteristics of miRNAs in osteogenesis provide an important step for their application in translational investigations of bone tissue engineering and bone disease.

Figure 1

miRNAs control the osteogenic differentiation of mesenchymal stem cells into osteoblasts. The microRNA above the green box indicates that they promote the osteogenic differentiation of mesenchymal stem cells into osteoblasts; the microRNAs listed below the green box indicates that they inhibit the osteogenic differentiation of mesenchymal stem cell into osteoblasts. miRNA/miR, microRNA.

Figure 2

MiR-548, miR-27, miR-346, miR-218, miR-34a, miR-21, miR-22 and miR-29b promote the osteogenic differentiation of mesenchymal stem cells through Wnt/catenin, Notch, TNF-α, TGF-β/BMP signaling pathways. miR, microRNA; PPAR-γ, peroxisome proliferator-activated receptor-γ; GSK-3β, glycogen synthase kinase-3β; Spry1, sprouty homolog 1; HDAC, histone deacetylase; DUSP2, dual specificity phosphatase 2; APC, adenomatous polyposis coli; SFRP2, secreted frizzled-related protein 2; DKK2, dickkopf WNT signaling pathway inhibitor 2; TCF, transcription factor; Runx2, runt-related transcription factor 2; OPN, osteopontin; OCN, osteocalcin; TNF-α, tumor necrosis factor-α; TGF-β, transforming growth factor-β; BMP, bone morphogenetic protein.

Figure 3

MicroRNAs suppress the osteogenic differentiation of mesenchymal stem cells through targeting transcription factors RUNX2, Smuf1, Osterix or BMP protein. miR, microRNA; Runx-2, runt-related transcription factor 2; BMP, bone morphogenetic protein; STAB2, stabilin 2; LRP6, lipoprotein receptor-related protein 6; Smad1, small mothers against decapentaplegic 1; SIRT1, silent information regulator 1; Smurf1, Smad ubiquitin regulatory factor 1; TAZ, transcriptional coactivator with PDZ-binding motif; MSX2, Msh homeobox 2; OPN, osteopontin; BSP, bone sialoprotein; OSX, osteoblast-specific transcription factor; OCN, osteocalcin.