bims-mirbon Biomed News
on MicroRNAs in Bone
Issue of 2021‒10‒17
seven papers selected by
Japneet Kaur
Mayo Clinic
  1. Characterization of Differentially Expressed miRNAs by CXCL12/SDF-1 in Human Bone Marrow Stromal Cells.
  2. Circ_0067680 expedites the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through miR-4429/CTNNB1/Wnt/β-catenin pathway.
  3. Long non-coding RNA RP11-84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR-23b-3p/RUNX2 axis.
  4. Bone marrow macrophage-derived exosomal miR-143-5p contributes to insulin resistance in hepatocytes by repressing MKP5.
  5. Live-cell imaging of microRNA expression with post-transcriptional feedback control.
  6. Bioinformatics Analysis Identified miR-584-5p and Key miRNA-mRNA Networks Involved in the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.
  7. HDAC6 Negatively Regulates miR-155-5p Expression to Elicit Proliferation by Targeting RHEB in Microvascular Endothelial Cells under Mechanical Unloading.
  1. Biomol Concepts. 2021 Oct 13. 12(1): 132-143
    Characterization of Differentially Expressed miRNAs by CXCL12/SDF-1 in Human Bone Marrow Stromal Cells.
    Matthew L Potter, Kathryn Smith, Sagar Vyavahare, Sandeep Kumar, Sudharsan Periyasamy-Thandavan, Mark Hamrick, Carlos M Isales, William D Hill, Sadanand Fulzele.
      Stromal cell-derived factor 1 (SDF-1) is known to influence bone marrow stromal cell (BMSC) migration, osteogenic differentiation, and fracture healing. We hypothesize that SDF-1 mediates some of its effects on BMSCs through epigenetic regulation, specifically via microRNAs (miRNAs). MiRNAs are small non-coding RNAs that target specific mRNA and prevent their translation. We performed global miRNA analysis and determined several miRNAs were differentially expressed in response to SDF-1 treatment. Gene Expression Omnibus (GEO) dataset analysis showed that these miRNAs play an important role in osteogenic differentiation and fracture healing. KEGG and GO analysis indicated that SDF-1 dependent miRNAs changes affect multiple cellular pathways, including fatty acid biosynthesis, thyroid hormone signaling, and mucin-type O-glycan biosynthesis pathways. Furthermore, bioinformatics analysis showed several miRNAs target genes related to stem cell migration and differentiation. This study's findings indicated that SDF-1 induces some of its effects on BMSCs function through miRNA regulation.
    Keywords:  SDF-1; bone marrow stromal cells; miRNA
    DOI:  https://doi.org/10.1515/bmc-2021-0015
  2. Biol Direct. 2021 Oct 14. 16(1): 16
    Circ_0067680 expedites the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through miR-4429/CTNNB1/Wnt/β-catenin pathway.
    Yuansheng Huang, Su Wan, Min Yang.
      BACKGROUND: Human bone marrow-derived mesenchymal stem cells (hBMSCs) are the primary source of osteoblasts in vivo. Emerging literatures have unveiled that circular RNAs (circRNAs) are actively drawn in the osteogenic differentiation of mesenchymal stem cells (MSCs). This research mainly illuminated the role of circ_0067680 as well as its regulatory mechanism in osteoblastic differentiation.METHODS: In this study, RT-qPCR was to measure the expression of circ_0067680. Functional assays were implemented to assess the role of circ_0067680 in osteogenic differentiation. Besides, RNA pull down, RIP and luciferase reporter assays were carried out to investigate the regulatory mechanism of circ_0067680.
    RESULTS: Circ_0067680, which derived from its host gene divergent protein kinase domain 2A (C3orf58), was up-regulated during osteogenic differentiation of hBMSCs. Besides, circ_0067680 deficiency impeded the osteoblastic differentiation of hBMSCs. Moreover, circ_0067680 served as a ceRNA via sequestering miR-4429 to regulate the expression of catenin beta 1 (CTNNB1), thereby activating the Wnt/β-catenin signaling pathway.
    CONCLUSION: Circ_0067680 accelerated hBMSCs osteogenic differentiation by the miR-4429/CTNNB1/Wnt/β-catenin signaling, which might be used as a potential biomarker for osteoblastic differentiation.
    Keywords:  CTNNB1; Osteogenic differentiation; Wnt/β-catenin signaling pathway; circ_0067680; miR-4429
    DOI:  https://doi.org/10.1186/s13062-021-00302-w
  3. Exp Ther Med. 2021 Nov;22(5): 1340
    Long non-coding RNA RP11-84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR-23b-3p/RUNX2 axis.
    Huaixi Yu, Yunyun Li, Jinshan Tang, Xiaoqing Lu, Wen Hu, Liang Cheng.
      The objective of the present study was to determine the role of RP11-84C13.1 in osteoporosis (OP) and its molecular mechanism. First, clinical samples were collected from OP patients and normal control patients. Human bone marrow stromal cells (hBMSCs) were extracted from femoral head tissues. Runt-related transcription factor 2 (RUNX2) and RP11-84C13.1 serum levels were assessed by reverse transcription-quantitative (RT-q)PCR. Following transfection of pcDNA-RP11-84C13.1, si-RP11-84C13.1, microRNA (miRNA)-23b-3p mimic and miRNA-23b-3p inhibitor, the expression levels of RUNX2 and RP11-84C13.1 were determined by RT-qPCR. In addition, the osteogenic ability of hBMSCs was assessed by Alizarin Red staining. The binding of RP11-84C13.1 to miRNA-23b-3p and the binding of miRNA-23b-3p to RUNX2 was confirmed by dual-luciferase reporter gene assay. Long non-coding RNA (lncRNA) RP11-84C13.1 was significantly downregulated in the serum of OP patients. The osteogenic differentiation-related genes RUNX2 and RP11-84C13.1 were markedly upregulated in a time-dependent manner, while the miRNA-23b-3p level gradually decreased in hBMSCs with the prolongation of osteogenesis. RP11-84C13.1 knockdown inhibited the osteogenic differentiation of hBMSCs. Furthermore, RP11-84C13.1 regulated RUNX2 expression by targeting miRNA-23b-3p. Overexpression of miRNA-23b-3p partially reversed the promoting effect of RP11-84C13.1 on the osteogenesis of hBMSCs. In conclusion, lncRNA RP11-84C13.1 upregulated RUNX2 by absorbing miRNA-23b-3p, and thus induced hBMSC osteogenesis to alleviate osteoporosis.
    Keywords:  Long noncoding RNA RP11-84C13.1; microRNA-23b-3p; osteoporosis; runt-related transcription factor 2
    DOI:  https://doi.org/10.3892/etm.2021.10775
  4. Cell Prolif. 2021 Oct 14. e13140
    Bone marrow macrophage-derived exosomal miR-143-5p contributes to insulin resistance in hepatocytes by repressing MKP5.
    Linfang Li, Huiyan Zuo, Xiuqing Huang, Tao Shen, Weiqing Tang, Xiaoyi Zhang, Tong An, Lin Dou, Jian Li.
      OBJECTIVE: In this study, we aim to explore the role of bone marrow macrophage-derived exosomes in hepatic insulin resistance, investigate the substance in exosomes that regulates hepatic insulin signalling pathways, reveal the specific molecular mechanisms involved in hepatic insulin resistance and further explore the role of exosomes in type 2 diabetes.MATERIALS AND METHODS: High-fat diet (HFD)-fed mice were used as obesity-induced hepatic insulin resistance model, exosomes were isolated from BMMs which were extracted from HFD-fed mice by ultracentrifugation. Exosomes were analysed the spectral changes of microRNA expression using a microRNA array. The activation of the insulin signalling pathway and the level of glycogenesis were examined in hepatocytes after transfected with miR-143-5p mimics. Luciferase assay and western blot were used to assess the target of miR-143-5p.
    RESULTS: BMMs from HFD-fed mice were polarized towards M1, and miR-143-5p was significantly upregulated in exosomes of BMMs from HFD-fed mice. Overexpression of miR-143-5p in Hep1-6 cells led to decreased phosphorylation of AKT and GSK and glycogen synthesis. Dual-luciferase reporter assay and western blot demonstrated that mitogen-activated protein kinase phosphatase-5 (Mkp5, also known as Dusp10) was the target gene of miR-143-5p. Moreover, the overexpression of MKP5 could rescue the insulin resistance induced by transfection miR-143-5p mimics in Hep1-6.
    CONCLUSION: Bone marrow macrophage-derived exosomal miR-143-5p induces insulin resistance in hepatocytes through repressing MKP5.
    Keywords:  MKP5; bone marrow macrophage; exosome; hepatic insulin resistance; miR-143-5p
    DOI:  https://doi.org/10.1111/cpr.13140
  5. Mol Ther Nucleic Acids. 2021 Dec 03. 26 547-556
    Live-cell imaging of microRNA expression with post-transcriptional feedback control.
    Masayuki Sano, Kana Morishita, Satoshi Oikawa, Takayuki Akimoto, Kimio Sumaru, Yoshio Kato.
      MicroRNAs (miRNAs) are small noncoding RNAs that regulate complex gene expression networks in eukaryotic cells. Because of their unique expression patterns, miRNAs are potential molecular markers for specific cell states. Although a system capable of imaging miRNA in living cells is needed to visually detect miRNA expression, very few fluorescence signal-on sensors that respond to expression of target miRNA (miR-ON sensors) are available. Here we report an miR-ON sensor containing a bidirectional promoter-driven Csy4 endoribonuclease and green fluorescent protein, ZsGreen1, for live-cell imaging of miRNAs with post-transcriptional feedback control. Csy4-assisted miR-ON (Csy4-miR-ON) sensors generate negligible background but respond sensitively to target miRNAs, allowing high-contrast fluorescence detection of miRNAs in various human cells. We show that Csy4-miR-ON sensors enabled imaging of various miRNAs, including miR-21, miR-302a, and miR-133, in vitro as well as in vivo. This robust tool can be used to evaluate miRNA expression in diverse biological and medical applications.
    Keywords:  Csy4; fluorescent protein; live-cell imaging; microRNA; post-transcriptional feedback control
    DOI:  https://doi.org/10.1016/j.omtn.2021.08.018
  6. Front Genet. 2021 ;12 750827
    Bioinformatics Analysis Identified miR-584-5p and Key miRNA-mRNA Networks Involved in the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.
    Chengze Wang, Lingling Dong, Ying Wang, Zhiwei Jiang, Jing Zhang, Guoli Yang.
      Human periodontal ligament cells (PDLCs) play an important role in periodontal tissue stabilization and function. In the process of osteogenic differentiation of PDLSCs, the regulation of molecular signal pathways are complicated. In this study, the sequencing results of three datasets on GEO were used to comprehensively analyze the miRNA-mRNA network during the osteogenic differentiation of PDLSCs. Using the GSE99958 and GSE159507, a total of 114 common differentially expressed genes (DEGs) were identified, including 62 up-regulated genes and 52 down-regulated genes. GO enrichment analysis was performed. The up-regulated 10 hub genes and down-regulated 10 hub genes were screened out by protein-protein interaction network (PPI) analysis and STRING in Cytoscape. Similarly, differentially expressed miRNAs (DEMs) were selected by limma package from GSE159508. Then, using the miRwalk website, we further selected 11 miRNAs from 16 DEMs that may have a negative regulatory relationship with hub genes. In vitro RT-PCR verification revealed that nine DEMs and 18 hub genes showed the same trend as the RNA-seq results during the osteogenic differentiation of PDLSCs. Finally, using miR-584-5p inhibitor and mimics, it was found that miR-584-5p negatively regulates the osteogenic differentiation of PDLSCs in vitro. In summary, the present results found several potential osteogenic-related genes and identified candidate miRNA-mRNA networks for the further study of osteogenic differentiation of PDLSCs.
    Keywords:  bioinformatics analysis; miR-584-5p; miRNA-mRNA networks; osteogenic differentiation; periodontal ligament stem cells
    DOI:  https://doi.org/10.3389/fgene.2021.750827
  7. Int J Mol Sci. 2021 Sep 29. pii: 10527. [Epub ahead of print]22(19):
    HDAC6 Negatively Regulates miR-155-5p Expression to Elicit Proliferation by Targeting RHEB in Microvascular Endothelial Cells under Mechanical Unloading.
    Liqun Xu, Lijun Zhang, Xiaoyan Zhang, Gaozhi Li, Yixuan Wang, Jingjing Dong, Honghui Wang, Zebing Hu, Xinsheng Cao, Shu Zhang, Fei Shi.
      Mechanical unloading contributes to significant cardiovascular deconditioning. Endothelial dysfunction in the sites of microcirculation may be one of the causes of the cardiovascular degeneration induced by unloading, but the detailed mechanism is still unclear. Here, we first demonstrated that mechanical unloading inhibited brain microvascular endothelial cell proliferation and downregulated histone deacetylase 6 (HDAC6) expression. Furthermore, HDAC6 promoted microvascular endothelial cell proliferation and attenuated the inhibition of proliferation caused by clinorotation unloading. To comprehensively identify microRNAs (miRNAs) that are regulated by HDAC6, we analyzed differential miRNA expression in microvascular endothelial cells after transfection with HDAC6 siRNA and selected miR-155-5p, which was the miRNA with the most significantly increased expression. The ectopic expression of miR-155-5p inhibited microvascular endothelial cell proliferation and directly downregulated Ras homolog enriched in brain (RHEB) expression. Moreover, RHEB expression was downregulated under mechanical unloading and was essential for the miR-155-5p-mediated promotion of microvascular endothelial cell proliferation. Taken together, these results are the first to elucidate the role of HDAC6 in unloading-induced cell growth inhibition through the miR-155-5p/RHEB axis, suggesting that the HDAC6/miR-155-5p/RHEB pathway is a specific target for the preventative treatment of cardiovascular deconditioning.
    Keywords:  HDAC6; RHEB; mechanical unloading; miR-155-5p; proliferation
    DOI:  https://doi.org/10.3390/ijms221910527
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