miR‐21 modulates the ERK–MAPK signaling pathway by regulating SPRY2 expression during human mesenchymal stem cell differentiation

Abstract

The ERK-MAPK signaling pathway plays a pivotal role during mesenchymal stem cell (MSC) differentiation. Studies have demonstrated that ERK-MAPK promotes adipogenesis and osteogenesis through the phosphorylation of differentiation-associated transcription factors and that it is the only active signaling in all three lineages (adipogenic, chondrogenic, and osteogenic) during MSC differentiation. Recent studies pointed to the significant roles of microRNA-21 (miR-21) during several physiological and pathological processes, especially stem cell fate determination. The miR-21 expression pattern is also correlated with ERK-MAPK activity. Here, we found that miR-21 expression is elevated and associated with an increased differentiation potential in MSCs during adipogenesis and osteogenesis. The overexpression of miR-21 elevated the expression level of the differentiation-associated genes PPARγ and Cbfa-1 during MSC differentiation, whereas miR-21 knockdown reduced the expression level of both genes. The ERK-MAPK signaling pathway activity had an increasing tendency to respond to miR-21 upregulation and a decreasing tendency to respond to miR-21 down-regulation during the first 4 days of adipogenesis and osteogenesis. Our data indicate that miR-21 modulated ERK-MAPK signaling activity by repressing SPRY2 expression, a known regulator of the receptor tyrosine kinase (RTK) signaling pathway, to affect the duration and magnitude of ERK-MAPK activity. The ERK-MAPK signaling pathway was regulated by Sprouty2 (SPRY2) expression via a miR-21-mediated mechanism during MSC differentiation.

Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

“…In this study, we found that the early markers of osteogenesis-related genes, including COLI, COLIII, RUNX2, OPN, and OCN, were upregulated compared with the levels obtained with the naked MAO Ti surface on days 3, 6, and 9, and this upregulation profile presented a time-dependent pattern and a dose-dependent effect. Our results indicated that the coating of CS/HA/miR-21 nanoparticles on the MAO Ti surface via reverse transfection promotes osteogenic differentiation at the mRNA level, which is in accordance with previous studies 16,17 that found that the overexpression of miR-21 can facilitate osteogenesis and accelerate bone fracture healing; furthermore, its target PI3K-AKT-GSK3β pathway may play an important role in the osteogenic differentiation of cells by stabilizing β-catenin according to previous reports. 17 This study confirmed the feasibility of fabricating CS/HA/miR-21 nanoparticle-coated MAO Ti surfaces via reverse transfection and demonstrated their application for the transfection of miR-21 to adjust the fate of hBMMSCs in vitro.…”

“…16 miR-21 has been found to be highly expressed during osteogenic differentiation, which indicates that this miRNA may repress stemness maintenance in osteoblasts. 16, 17 Ourania et al 18 and Meng et al 17 revealed that the overexpression of miR-21 can accelerate osteogenesis and impair adipogenesis in both human umbilical cord mesenchymal stem cells (MSCs) and human bone marrow MSCs (hBMMSCs); miR-21 may exert its osteogenic function through the PI3K-AKT-GSK3β pathway via the stabilization and accumulation of β-catenin. 17 A key issue in the therapeutic application of miRNAs is safe and highly efficient transfection.…”

“…35 miR-21 has been widely studied and may induce the upregulation of the expression of osteogenesisrelated genes. 16 In this work, we used CS/HA nanoparticles to stabilize, store, and deliver miR-21 in a controlled manner and explored appropriate CS/HA/miR-21 nanoparticles with a CS/HA ratio of 4:1 and N/P ratio of 20:1 for better transfection. We then fabricated CS/HA/miR-21 nanoparticle-coated MAO Ti surfaces through cross-linking using a 0.2% gel solution as a type of reverse transfection.…”

Mnk1 (Mitogen-Activated Protein Kinase–Interacting Kinase 1) Deficiency Aggravates Cardiac Remodeling in Mice

“…Recent studies have pointed out the significant role of sprouty2, a substrate of Mnk1, during multiple diseases or physiological process such as human mesenchymal stem cell differentiation, 17 papillary thyroid cancer, 18 and prostate cancer progression 19 by regulating ERK signaling pathway. ERK1/2 is one of the most important signaling that could provide new treatment strategies for cardiac hypertrophy and remodeling.…”

MicroRNA expression profiles in liver and colon of sexually immature gilts after exposure to Fusarium mycotoxins

“…In pigs, predicted mRNA targets include among others programmed cell death protein 4 (PDCD4) or ineterleukin 10 (IL10) that further regulate a set of genes critical to cell proliferation and inflammation (Podolska et al 2012). Interestingly, in many cell types miR-21 expression pattern is correlated with ERK-MAPK activity (Mei et al 2013), the intracellular signaling pathways inducing a variety of downstream processes. It was found recently, that DON, besides its effects on cell differentiation and proliferation, may affect the intestinal barrier function through MAPK and claudin proteins (Pinton et al 2009).…”