miR-449a Regulates the Chondrogenesis of Human Mesenchymal Stem Cells Through Direct Targeting of Lymphoid Enhancer-Binding Factor-1

Paik, So Ya; Jung, Ho Sun; Lee, Seulgi; Yoon, Dong Suk; Park, Min Sung; Lee, Jin Woo

doi:10.1089/scd.2011.0732

Cited by 45 publications

(30 citation statements)

References 46 publications

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“…MiR-449 negatively regulates chondrocyte differentiation of MSCs [51]. In human bone marrow MSCs and in human chondrosarcoma cell lines, miR-449 suppresses Lef1, a critical component of the Wnt signaling pathway.…”

Section: Mirnas In the Chondrocyte Differentiation Of Stem Cellsmentioning

confidence: 99%

MicroRNAs involved in bone formation

Papaioannou

Mirzamohammadi

Kobayashi

2014

Cell. Mol. Life Sci.

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During skeletal development, mesenchymal progenitor cells undergo a multistage differentiation process in which they proliferate and become bone- and cartilage-forming cells. This process is tightly regulated by multiple levels of regulatory systems. The small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate gene expression. Recent studies have demonstrated that miRNAs play significant roles in all stages of bone formation, suggesting the possibility that miRNAs can be novel therapeutic targets for skeletal diseases. Here, we review the role and mechanism of action of miRNAs in bone formation. We discuss roles of specific miRNAs in major types of bone cells, osteoblasts, chondrocytes, osteoclasts, and their progenitors. Except a few, the current knowledge about miRNAs in bone formation has been obtained mainly by in vitro studies; further validation of these findings in vivo is awaited. We also discuss about several miRNAs of particular interest in the light of future therapies of bone diseases.

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Section: Mirnas In the Chondrocyte Differentiation Of Stem Cellsmentioning

confidence: 99%

MicroRNAs involved in bone formation

Papaioannou

Mirzamohammadi

Kobayashi

2014

Cell. Mol. Life Sci.

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“…miR-199a is a well-known BMP2-responsive microRNA and a regulator of chondrogenic differentiation via targeting smad1 [26]. Further, our previous report showed that LEF-1 promotes chondrogenic differentiation of hMSCs and revealed that miR-449a regulates LEF-1 expression [27]. Although microRNAs regulating chondrogenesis have been reported, it was not reported whether microRNAs regulate chondrogenic differentiation of human mesenchymal stem cells (hMSCs) by directly targeting Sox9 expression.…”

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confidence: 99%

microRNA-495 Inhibits Chondrogenic Differentiation in Human Mesenchymal Stem Cells by TargetingSox9

Lee

Yoon

Paik

et al. 2014

Stem Cells and Development

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The chondrogenic differentiation process of human mesenchymal stem cells (hMSCs) passes through multiple stages, which are carried out by various factors and their interactions. Recently, microRNAs that regulate chondrogenic differentiation have been reported. However, microRNA that regulates SRY-related high mobility group-box gene 9 (Sox9), a chondrogenic key factor, has not been identified in hMSC. In this study, we identified that microRNA-495 (miR-495) is an important regulator of hMSC chondrogenic differentiation. In our microarray, miR-495 was downregulated during transforming growth factor (TGF)-b3-induced chondrogenic differentiation of hMSCs in vitro. We found that there is an miR-495 binding site in the 3¢ untranslated region (3¢UTR) of Sox9. We confirmed opposite expression between miR-495 and Sox9 by using real-time polymerase chain reaction. Further, overexpression of miR-495 inhibited Sox9 expression, and repression of miR-495 increased expression of Sox9 in SW1353 cells and hMSCs. Additionally, luciferase analysis revealed that miR-495 directly binds to the Sox9 3¢UTR, and we confirmed a seed sequence of miR-495 on the Sox9 3¢UTR. Subsequently, overexpression of miR-495 repressed the expression of the extracellular matrix (ECM) protein, such as type II collagen (Col2A1), aggrecan, and proteoglycan products, whereas inhibition of miR-495 increased their expression. Collectively, this study indicates that miR-495 directly targets Sox9, ultimately leading to the regulation of chondrogenic differentiation in hMSCs.

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“…Mesenchymal stem cells (MSCs) are pluripotent adult stem cells that can be induced to differentiate into various mesenchymal lineages, including osteocytes, chondrocytes and adipocytes [33][34][35], and other lineages [36], such as neurons [37] and astrocytes [38]. Because of their ability to transdifferentiate across embryonic boundaries into neuronal cells, MSCs are considered good potential candidates for treating neurodegenerative disorders and nerve injury diseases [32].…”

Section: Discussionmentioning

confidence: 99%

Neurotrophine-3 may contribute to neuronal differentiation of mesenchymal stem cells through the activation of the bone morphogenetic protein pathway

Liu

Jiang

2015

Cellular and Molecular Biology Letters

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We investigated whether neurotrophin-3 (NT-3) can promote differentiation of mouse bone mesenchymal stem cells (MSCs) into neurons via the bone morphogenetic protein pathway. MSCs were prepared from rat bone marrow and either transfected with pIRES2-EGFP or pIRES2-EGFP-NT-3 or treated with bone morphogenetic protein 4. The pIRES2-EGFP-NT-3-transfected MSCs further underwent noggin treatment or siRNA-mediated knockout of the TrkC gene or were left untreated. Immunofluorescence staining, real-time PCR and Western blot analyses were performed to evaluate the transcription and expression of neural-specific genes and BMP-Smad signaling. MSCs were efficiently transduced by the NT-3 gene via pIRES2-EGFP vectors. pIRES2- EGFP-NT-3 could initiate the transcription and expression of neural-specific genes, including nestin, NSE and MAP-2, and stimulate BMP-Smad signaling. The transcription and expression of neural-specific genes and BMP-Smad signaling were significantly suppressed by siRNA-mediated knockdown of the TrkC gene of MSCs. These findings suggest that the BMP signaling pathway may be a key regulatory point in NT-3-transfected neuronal differentiation of MSCs. The BMP and neurotrophin pathways contribute to a tightly regulated signaling network that directs the precise connections between neuronal differentiation of MSCs and their targets.

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miR-449a Regulates the Chondrogenesis of Human Mesenchymal Stem Cells Through Direct Targeting of Lymphoid Enhancer-Binding Factor-1

Cited by 45 publications

References 46 publications

MicroRNAs involved in bone formation

MicroRNAs involved in bone formation

microRNA-495 Inhibits Chondrogenic Differentiation in Human Mesenchymal Stem Cells by TargetingSox9

Neurotrophine-3 may contribute to neuronal differentiation of mesenchymal stem cells through the activation of the bone morphogenetic protein pathway

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