The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling

Ham, Ok Kyung; Song, Bomi; Lee, Se Yeon; Choi, Eunmi; Ji, Min; Lee, Chang Youn; Park, Jun Hee; Kim, Il Kwon; Chang, Won Hyuk; Lim, Soyeon; Lee, Young Moo; Kim, Soonhag; Jang, Yangsoo; Hwang, Ki Chul

doi:10.1016/j.biomaterials.2012.03.025

Cited by 98 publications

(69 citation statements)

References 26 publications

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“…The miRNA miR-675 can promote chondrogenic differentiation by inducing the expression of cartilage-specific collagen type Ⅱa through the positive regulation of cartilage-specific Sox9 [133] . The chondrogenic differentiation of MSCs is induced by miR-23b, which negatively inhibits of protein kinase A signaling [134] . In addition, miR-18a, miR-199a, miR-145, and miR-221 have been identified as negative regulators of chondrogenesis.…”

Section: Osteoblast Osteoclast and Chondrocyte Differentiationmentioning

confidence: 99%

“…The fate of HSCs is regulated by small molecules that promote self-renewal [181][182][183] . Using small molecules, multipotent MSCs can differentiate into various non-hematopoietic cells, such as chondrocytes [134,184] , osteoblasts [185,186] , hepatocytes [187] , cardiomyocytes [188,189] , adipocytes [190,191] and neuronal-like cells [192][193][194] . Additionally, the maintenance of MSCs is associated with the Wnt signaling pathway [195,196] .…”

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

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MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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Section: Osteoblast Osteoclast and Chondrocyte Differentiationmentioning

confidence: 99%

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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“…However, expression of MSC-positive markers such as CD44, CD73, and CD90 was increased (Chang et al, 2013). We previously showed that treatment of human bone marrow derived MSCs (BMMSCs) with the small molecule protein kinase A (PKA) inhibitor H-89 results in their differentiation into chondrocytes (Ham et al, 2012). To extend these results, we measured absorbance of alcian blue in SFMSCs and compared it to that of BMMSCs.…”

Section: Resultsmentioning

confidence: 99%

“…The short oligonucleotide had the sequence Rev-3′- GTTACACTA -5′– BHQ1. The oligonucleotides were manufactured by Bionics (Korea) (Ham et al, 2012). …”

Section: Methodsmentioning

confidence: 99%

Upregulation of miR-23b Enhances the Autologous Therapeutic Potential for Degenerative Arthritis by Targeting PRKACB in Synovial Fluid-Derived Mesenchymal Stem Cells from Patients

Ham

Lee

Song

et al. 2014

Molecules and Cells

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The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23btransfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.

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“…In vitro studies have identified several miRNAs related to the MSC chondrogenic differentiation, including negative regulators miR-145 and miR-449a [54, 55] and positive regulator miR-23b [56]. MiR-449a could repress expression of SOX9, the essential transcription factor for chondrogenesis, leading to delayed progression of chondrogenesis while positive regulator could promote chondrogenic differentiation of human MSCs by inhibiting protein kinase A (PKA) signaling [55].…”

Section: Therapeutic Prospect Of Microrna In Regenerative Medicinementioning

confidence: 99%

MicroRNA delivery for regenerative medicine

Peng

Chen

Leong

2015

Advanced Drug Delivery Reviews

133

112

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MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages and disadvantages. A number of studies have demonstrated success in augmenting osteogenesis, improving cardiogenesis, and reducing fibrosis among many other tissue engineering applications. A scaffold-based approach with the possibility of local and sustained delivery of miRNA is particularly attractive since the physical cues provided by the scaffold may synergize with the biochemical cues induced by miRNA therapy. Herein, we first briefly cover the application of miRNA to direct stem cell fate via replacement and inhibition therapies, followed by the discussion of the promising viral and nonviral delivery systems. Next we present the unique advantages of a scaffold-based delivery in achieving lineage-specific differentiation and tissue development.

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The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling

Cited by 98 publications

References 26 publications

MicroRNAs as novel regulators of stem cell fate

MicroRNAs as novel regulators of stem cell fate

Upregulation of miR-23b Enhances the Autologous Therapeutic Potential for Degenerative Arthritis by Targeting PRKACB in Synovial Fluid-Derived Mesenchymal Stem Cells from Patients

MicroRNA delivery for regenerative medicine

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