Sox4 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cell via activation of long noncoding RNA DANCR

Zhang, Lei; Chen, Shuo; Bao, Nirong; Yang, Chao; Ti, Yunfan; Zhou, Lei; Zhao, Jianning

doi:10.1007/s10735-015-9638-z

Cited by 39 publications

(30 citation statements)

References 23 publications

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“…SMSCs have shown promising efficiency for cell-based regeneration of damaged articular cartilage [14]. Our previous data demonstrated that chondrogenic differentiation of SMSCs was promoted by lncRNA DANCR [12,13]. In the present study, we characterized the underlying molecular mechanism that overexpression of DANCR down-regulates miR-1305 .…”

Section: Discussionmentioning

confidence: 77%

“…Informed consents were obtained from the patients. The protocol for SMSCs isolation was established as previously described [13]. Briefly, synovial tissue was collected from the patients with osteoarthritis during the operations.…”

Section: Methodsmentioning

confidence: 99%

“…Mature miRNAs regulate genes through complementary interactions with the 3′-UTR region of mRNA, resulting in the degradation of mRNA or inhibition of protein translation [25]. Several miRNAs have been demonstrated to be involved in chondrogenic differentiation of MSCs [13,29–33]. Amongst these, miR-410 was reported to promote the chondrogenic differentiation through Wnt signaling pathway [34].…”

Section: Introductionmentioning

confidence: 99%

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Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells

et al. 2017

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miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305, which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-β pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305-Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.

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Section: Discussionmentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells

et al. 2017

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“…Another recent study identified that the transcription factor, SOX4, can regulate the proliferation and chondrogenic differentiation of human synovium-derived MSCs (SMSCs) and that activation of the IncRNA, DANCR , is involved in this process (90). Here, SMSCs were extracted from the synovium of osteoarthritis (OA) patients and aggregate cultures were utilized for in vitro chondrogenesis.…”

Section: Incrnas Regulating Chondrocyte Differentiationmentioning

confidence: 99%

Emerging roles for long noncoding RNAs in skeletal biology and disease

Huynh

Anderson

Guilak

et al. 2016

Connective Tissue Research

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Normal skeletal development requires tight coordination of transcriptional networks, signaling pathways, and biomechanical cues, and many of these pathways are dysregulated in pathological conditions affecting cartilage and bone. Recently, a significant role has been identified for long noncoding RNAs (IncRNAs) in developing and maintaining cellular phenotypes, and improvements in sequencing technologies have led to the identification of thousands of IncRNAs across diverse cell types, including the cells within cartilage and bone. It is clear that IncRNAs play critical roles in regulating gene expression. For example, they can function as epigenetic regulators in the nucleus via chromatin modulation to control gene transcription, or in the cytoplasm, where they can function as scaffolds for protein-binding partners or modulate the activity of other coding and noncoding RNAs. In this review, we discuss the growing list of IncRNAs involved in normal development and/or homeostasis of the skeletal system, the potential mechanisms by which these IncRNAs might function, and recent improvements in the methodologies available to study IncRNA functions in vitro and in vivo. Finally, we address the likely utility of IncRNAs as biomarkers and therapeutic targets for diseases of the skeletal system, including osteoarthritis, osteoporosis, and in cancers of the skeletal system.

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“…With further analyses to find biological function of lncRNAs and their involvement in the mechanism of differentiation, it has been determined that two ZBED3-AS1 and CTA-941F9.9 lncRNAs are most likely playing important roles in chondrogenic differentiation process (4). Several other reports focused on the findings about the regulatory roles of lncRNAs in self-renewal and differentiation into any lineage, and explained the underlying molecular mechanisms (5,6 (8). Moreover, lncRNA H19 promotes osteoblast differentiation of hMSCs Via TGF-β1/Smad3/HDAC signaling pathway by deriving miR-675 and may serve as a potential target for enhancing bone formation in vivo (9).…”

mentioning

confidence: 99%

Significance of Long Noncoding RNAs in Regenerative Medicine

Amirkhah¹

2016

CTRM

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Stem cells are considered as the promising candidates to regenerate damaged tissues. A number of clinical trials have encouraged the researchers and clinicians to use stem cells especially mesenchymal stem cells (MSCs) due to its several unique properties. These cells, in addition to multilinage differentiation potential and high proliferation capacity, exert paracrine effects via the release of exosomes and microvesicles which are known as the main mediators of cell to cell communication (Figure 1). The concept that lncRNAs might be paracrine or even endocrine effectors, is based on the evidence that they can transport via extracellular vesicles (EVs), i.e. exosomes and microvesicles (MVs) between cells, either within a surrounding tissue or remotely by entering into blood (1, 2). It has been shown that the EVs may contain mRNA, noncoding RNA (microRNA, LncRNA, and etc) and sometimes even DNA, in addition to lipids and proteins; secreting from the stem cells and having the capacity to alter the phenotype and cell fate of neighboring cells to restore injury tissues/organs (2, 3). Recently, Wang et al. have investigated the expression profiles of lncRNAs

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Sox4 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cell via activation of long noncoding RNA DANCR

Cited by 39 publications

References 23 publications

Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells

Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells

Emerging roles for long noncoding RNAs in skeletal biology and disease

Significance of Long Noncoding RNAs in Regenerative Medicine

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