Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway

Deng, Lidi; Hong, Hong; Zhang, Xueqin; Chen, Dongru; Chen, Zhengyuan; Ling, Junqi; Wu, Liping

doi:10.1016/j.bbrc.2018.07.160

Cited by 70 publications

(63 citation statements)

References 27 publications

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“…Recently reports have also demonstrated that lncRNA could serve as epigenetic regulators participating in the osteogenic differentiation of MSC. For example, lncRNA MEG3 inhibited osteogenic differentiation of human dental follicle stem cells by epigenetically regulating wnt pathway [30]. HoxA-AS3 was reported to act as an epigenetic switch through binding with EZH2 and inhibit the transcription of key osteoblastic factors in bone marrow mesenchymal stem cells [31].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic silencing of KLF2 by long non-coding RNA SNHG1 inhibits periodontal ligament stem cell osteogenesis differentiation

Guo

2020

Stem Cell Res Ther

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Background Exploring the effects of lncRNA SNHG1 in the process of osteogenic differentiation of periodontal ligament stem cells (PDLSCs) would provide novel therapeutic strategies for tissue regeneration. Methods Loss-of-function and gain-of-function assays were induced by lentivirus. The osteogenic differentiation of PDLSCs were assessed by ALP staining and Alizarin Red staining as well as the mRNA and protein levels of osteogenic marker genes osterix, osteocalcin, and alkaline phosphatase through qRT-PCR and western blot. RNA immunoprecipitation assay and chromatin immunoprecipitation assays were performed to uncover the interaction between SNHG1 and EZH2. Results Our analysis revealed that SNHG1 was downregulated and KLF2 was upregulated during the osteogenic induction differentiation of PDLSCs. SNHG1 inhibited while KLF2 promoted osteogenic differentiation of PDLSCs. SNHG1 directly interact with the histone methyltransferase enhancer of the zeste homolog 2 (EZH2) and modulate the histone methylation of promoter of Kruppel-like factor 2 (KLF2) and altered the progress osteogenic differentiation of PDLSCs. Conclusions Taken together, SNHG1 inhibited the osteogenic differentiation of PDLSCs through EZH2-mediated H3K27me3 methylation of KLF2 promotor and provided a novel class of therapeutic targets for regenerate dental tissues.

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Section: Discussionmentioning

confidence: 99%

Epigenetic silencing of KLF2 by long non-coding RNA SNHG1 inhibits periodontal ligament stem cell osteogenesis differentiation

Guo

2020

Stem Cell Res Ther

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“…Previous reports have indicated a positive correlation with human diseases showing abnormal differentiation of BM-MSCs [29]. In one report, MEG3 inhibits of cell proliferation and down regulation of MEG3 activates the Wnt/beta-catenin signaling pathway via epigenetically regulating Wnt genes promotor [30]. Another study demonstrated that down regulation of MEG3 promotes BM-MSCs differentiation [31].…”

Section: Discussionmentioning

confidence: 96%

Response Relating Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis

Gupta¹,

Youn²,

Han³

et al. 2019

Preprint

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Liver cirrhosis leads to hepatic dysfunction and life-threatening conditions. Though clinical efficacy of autologous bone marrow-derived mesenchymal stem cells (BM-MSC) transplantation in alcoholic cirrhosis (AC) was demonstrated, the relevant mechanism has not been elucidated. We aimed to identify predictive factors and gene/pathways for responders after autologous BM-MSC transplantation. Fifty-five patients with biopsy-proven AC underwent autologous BM-MSC transplantation. The characteristics of responders who showed improvement in Laennec score (≥ 1) after transplantation were compared with those of non-responders. BM-MSCs were analyzed with cDNA microarrays to identify gene/pathways that were differentially expressed in responder. Thirty-three patients (66%) were responders. Initial high Laennec score (p=0.007, odds ratio 3.73) and performance of BM-MSC transplantation (p=0.033, odds ratio 5.75) were predictive factors for responder. Three genes (olfactory receptor2L8, microRNA4520-2, and chloride intracellular channel protein3) were upregulated in responders and CD36 and retinol-binding protein 4 are associated with biologic processes dominant in non-responder. Eleven pathways (inositol phosphate, ATP-binding cassette transporters, protein-kinase signaling, extracellular matrix-receptor interaction, endocytosis, phagosome, hematopoietic cell lineage, adipocytokine, peroxisome proliferator-activated receptor, fat digestion/absorption, and insulin resistance) were upregulated in non-responders (p<0.05). BM-MSC transplantation is warranted treatment for AC patients with high Laennec score. Cell-based therapy utilizing response-relating genes or pathway can be treatment candidate.

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“…Moreover, EZH2 can directly inhibit the expression of Wnt genes such as β-catenin and Wnt ligand expression through H3K27 trimethylation. Elevated levels of MEG3 increases EZH2 expression, and attenuates osteogenic differentiation by inhibiting the Wnt/β-catenin signaling pathway in human dental follicle stem cells (19).…”

Section: Roles Of Lncrna Meg3 In Osteogenic Differentiationmentioning

confidence: 98%

Long non‑coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review)

Sun

Peng

et al. 2020

Biomed Rep

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Osteogenic differentiation originating from mesenchymal stem cells (MSCs) requires tight coordination of transcriptional factors, signaling pathways and biomechanical cues. Dysregulation of such reciprocal networks may influence the proliferation and apoptosis of MSCs and osteoblasts, thereby impairing bone metabolism and homeostasis. An increasing number of studies have shown that long non-coding (lnc)RNAs are involved in osteogenic differentiation and thus serve an important role in the initiation, development, and progression of bone diseases such as tumors, osteoarthritis and osteoporosis. It has been reported that the lncRNA, maternally expressed gene 3 (MEG3), regulates osteogenic differentiation of multiple MSCs and also acts as a critical mediator in the development of bone formation and associated diseases. In the present review, the proposed mechanisms underlying the roles of MEG3 in osteogenic differentiation and its potential effects on bone diseases are discussed. These discussions may help elucidate the roles of MEG3 in osteogenic differentiation and highlight potential biomarkers and therapeutic targets for the treatment of bone diseases. Contents 1. Introduction 2. Roles of lncRNA MEG3 in osteogenic differentiation 3. Roles of lncRNA MEG3 in bone diseases 4. Conclusion

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Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway

Cited by 70 publications

References 27 publications

Epigenetic silencing of KLF2 by long non-coding RNA SNHG1 inhibits periodontal ligament stem cell osteogenesis differentiation

Epigenetic silencing of KLF2 by long non-coding RNA SNHG1 inhibits periodontal ligament stem cell osteogenesis differentiation

Response Relating Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis

Long non‑coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review)

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