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MiR-137-mediated negative relationship between LGR4 and RANKL modulated osteogenic differentiation of human adipose-derived mesenchymal stem cells

Genetics and molecular biology, 2022-01, Vol.45 (3), p.1-e20210322 [Peer Reviewed Journal]

Copyright Sociedade Brasileira de Genetica 2022 ;This work is licensed under a Creative Commons Attribution 4.0 International License. ;ISSN: 1415-4757 ;ISSN: 1678-4685 ;EISSN: 1678-4685 ;DOI: 10.1590/1678-4685-GMB-2021-0332 ;PMID: 36121915

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  • Title:
    MiR-137-mediated negative relationship between LGR4 and RANKL modulated osteogenic differentiation of human adipose-derived mesenchymal stem cells
  • Author: Fan, Cong ; Li, Yulong
  • Subjects: BIOCHEMISTRY & MOLECULAR BIOLOGY ; Cell lines ; Cellular, Molecular and Developmental Genetics ; Crosstalk ; Differentiation (biology) ; Epigenetics ; Gene expression ; Genes ; GENETICS & HEREDITY ; human adipose-derived mesenchymal stem cells ; Leucine ; LGR4 ; Mesenchyme ; MicroRNA ; miRNA ; Osteogenesis ; osteogenic differentiation ; RANKL ; Receptors ; Stem cells ; TRANCE protein
  • Is Part Of: Genetics and molecular biology, 2022-01, Vol.45 (3), p.1-e20210322
  • Description: MicroRNA-137 (miR-137) has recently emerged as an osteogenic regulator in several cell lines. This study aimed to identify the function of miR-137 on the crosstalk between leucine rich repeat containing G protein-coupled receptor 4 (LGR4) and receptor activator of nuclear factor-κB ligand (RANKL), thus unveiling the critical role of LGR4-RANKL interplay in the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs). By examining the osteogenic capacity and possible downstream genes expression with miR-137 overexpression/knockdown, we found that miR-137 downregulated LGR4 while upregulating RANKL. According to the results of dual-luciferase reporter assay, LGR4 was validated as a direct target of miR-137. Surprisingly, a negative relationship between LGR4 and RANKL was confirmed by the knockdown of these two genes. Furthermore, RANKL inhibitor could alleviate or reverse the inhibitory effects on osteogenesis generated by LGR4 knockdown. Collectively, this study indicated that miR-137-induced a negative crosstalk between LGR4 and RANKL that could contribute to the osteogenic regulation of hASCs and provide more systematic and in-depth understanding of epigenetic modulation by miR-137.
  • Publisher: Ribeirao Preto: Sociedade Brasileira de Genetica
  • Language: English;Portuguese
  • Identifier: ISSN: 1415-4757
    ISSN: 1678-4685
    EISSN: 1678-4685
    DOI: 10.1590/1678-4685-GMB-2021-0332
    PMID: 36121915
  • Source: SciELO
    GFMER Free Medical Journals
    PubMed Central
    DOAJ Directory of Open Access Journals
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