The Role of lncRNAs in Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Wang, Jicheng; Liu, Shizhang; Shi, Jiyuan; Liu, Huitong; Li, Jingyuan; Zhao, Song; Zhi, Yi

doi:10.2174/1574888x15666191227113742

Cited by 28 publications

(19 citation statements)

References 66 publications

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“…Growing amounts of evidences have shown that lncRNAs are important regulators in diverse biological processes and diseases including osteoporosis 5 – 7 . A good number of lncRNAs have been demonstrated to play critical roles in the osteogenic differentiation of BMSCs 8 – 10 . For example, lncRNA MALAT1 was downregulated in BMSCs from osteoporosis rats compared with the normal rats, and could inhibit osteogenesis through MAPK signaling 11 .…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

et al. 2020

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Osteoporosis is a prevalent metabolic bone disease characterized by low bone mineral density and degenerative disorders of bone tissues. Previous studies showed the abnormal osteogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) contributes to the development of osteoporosis. However, the underlying mechanisms by which BMSCs undergo osteogenic differentiation remain largely unexplored. Recently, long non-coding RNAs have been discovered to play important roles in regulating BMSC osteogenesis. In this study, we first showed MIR22HG, which has been demonstrated to be involved in the progression of several cancer types, played an important role in regulating BMSC osteogenesis. We found the expression of MIR22HG was significantly decreased in mouse BMSCs from the osteoporotic mice and it was upregulated during the osteogenic differentiation of human BMSCs. Overexpression of MIR22HG in human BMSCs enhanced osteogenic differentiation, whereas MIR22HG knockdown inhibited osteogenic differentiation both in vitro and in vivo. Mechanistically, MIR22HG promoted osteogenic differentiation by downregulating phosphatase and tensin homolog (PTEN) and therefore activating AKT signaling. Moreover, we found MIR22HG overexpression promoted osteoclastogenesis of RAW264.7 cells, which indicated that MIR22HG played a significant role in bone metabolism and could be a therapeutic target for osteoporosis and other bone-related diseases.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

et al. 2020

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“…There is accumulating evidence that microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are closely related to the occurrence and development of various diseases, including in ammatory diseases, metabolic diseases, and cancer [57][58][59]. Long non-coding RNA (lncRNA) is an RNA molecule greater than 200 nucleotides in length and recent studies have also shown that lncRNAs play an important role in the osteogenic differentiation of BMMSCs [60][61][62]. Growing research has demonstrated that lncRNA modulates gene expression at multiple levels such as epigenetic, transcriptional and post transcriptional [63].…”

Section: Discussionmentioning

confidence: 99%

LncRNA H19 from T-Regulatory-Cell-Derived Exosomes Sponges miR-154-5p to Promote Osteogenic Differentiation of BMMSCs Through Upregulating POSTN

Zhang

Liu

et al. 2021

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Background: Mesenchymal stem cells (MSCs) can play an important role in anti-inflammatory function because it can induce Treg cells formation. Recent studies have confirmed that Tregs can release exosomes and induce immune tolerance as important immune cells. Thus, to clarify the function and regulatory mechanism of Treg cells-derived exosomes on osteogenic differentiation of BMMSCs is very important.Methods: CD4+ T cells isolated from mouse spleens were induced into CD4+ Foxp3+ Treg cells and co-cultured with BMMSCs. Then we isolated exosomes derived from Treg cells and tracked the exosomes using fluorescent labeling PKH67.Starbase, miRWalk, targetscan, bioinformatics analysis and functional complementation experiments to find relative lncRNA-miRNAs which involed in osteogenic differentiation of BMMSCs.Results: We found that exosomes derived from Tregs could enter BMMSCs and the expression of osteoblast-related genes were significantly up-regulated compared to the BMMSCs co-cultured with naïve T cells. LncRNA H19 from Tregs-derived exosomes could affect the osteogenic differentiation of BMMSCs in vitro by regulating POSTN expression via sponge miR-154-5p.Conclusions: This study demonstrated that important role of exosomes from Tregs in regulating osteogenic differentiation of BMMSCs. lncRNA H19 from Tregs-derived exosomes plays a positive regulatory role in osteogenic differentiation of BMMSCs through miR-154-5p/POSTN axis. It might has important clinical implications for inflammatory diseases and exosomes released from Tregs could be used as a new type of immunoregulation reagent for the treatment of periodontitis.

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“…As an important subset of non-coding RNAs (ncRNAs), long ncRNAs (lncRNAs) exceeding 200 nucleotides in length play important roles in various biological and pathological processes including osteogenesis [ 3 ] and the osteogenic differentiation of hBMSCs [ 4 – 6 ]. A recent study showed that lncRNA MIR22HG promotes osteogenic differentiation by downregulating phosphatase and tensin homolog, thereby activating AKT signaling [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway

et al. 2022

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Background The treatment of bone loss has posed a challenge to clinicians for decades. Thus, it is of great significance to identify more effective methods for bone regeneration. However, the role and mechanisms of long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) during osteogenic differentiation remain unclear. Methods We investigated the function of SNHG5, Yin Yang 1 (YY1), miR-212-3p and growth differentiation factor 5 (GDF5) in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo. Molecular mechanisms were clarified by chromatin immunoprecipitation assay and dual luciferase reporter assay. Results We found SNHG5 expression was upregulated during osteogenesis of hBMSCs. Knockdown of SNHG5 in hBMSCs inhibited osteogenic differentiation while overexpression of SNHG5 promoted osteogenesis. Moreover, YY1 transcription factor directly bound to the promoter region of SNHG5 and regulated SNHG5 expression to promote osteogenesis. Dual luciferase reporter assay confirmed that SNHG5 acted as a miR-212-3p sponge and miR-212-3p directly targeted GDF5 and further activated Smad1/5/8 phosphorylation. miR-212-3p inhibited osteogenic differentiation, while GDF5 promoted osteogenic differentiation of hBMSCs. In addition, calvarial defect experiments showed knockdown of SNHG5 and GDF5 inhibited new bone formation in vivo. Conclusion Our results demonstrated that the novel pathway YY1/SNHG5/miR-212-3p/GDF5/Smad regulates osteogenic differentiation of hBMSCs and may serve as a potential target for the treatment of bone loss.

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The Role of lncRNAs in Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Cited by 28 publications

References 66 publications

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

LncRNA H19 from T-Regulatory-Cell-Derived Exosomes Sponges miR-154-5p to Promote Osteogenic Differentiation of BMMSCs Through Upregulating POSTN

Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway

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