miR-31-5p Is a LIPUS-Mechanosensitive MicroRNA that Targets HIF-1α Signaling and Cytoskeletal Proteins

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The roles of low-intensity pulsed ultrasound (LIPUS) and microRNAs (miRNAs) on hMSCs commitments have already been investigated; however, the effects of the application of their co-treatments in an in vitro cell model are still unknown. Our previous studies demonstrated that (i) LIPUS modulated hMSCs cytoskeletal organization and (ii) miRNA-675-5p have a role in HIF-1α signaling modulation during hMSCs osteoblast commitment. We investigated for the first time the role of LIPUS as promoter tool for miRNA expression. Thanks to bioinformatic analysis, we identified miR-31-5p as a LIPUS-induced miRNA and investigated its role through in vitro studies of gain and loss of function. Results highlighted that LIPUS stimulation induced a hypoxia adaptive cell response, which determines a reorganization of cell membrane and cytoskeleton proteins. MiR-31-5p gain and loss of function studies, demonstrated as miR-31-5p overexpression, were able to induce hypoxic and cytoskeletal responses. Moreover, the co-treatments LIPUS and miR-31-5p inhibitor abolished the hypoxic responses including angiogenesis and the expression of Rho family proteins. MiR-31-5p was identified as a LIPUS-mechanosensitive miRNAs and may be considered a new therapeutic option to promote or abolish hypoxic response and cytoskeletal organization on hMSCs during the bone regeneration process.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Issue number7
Publication statusPublished - Mar 28 2019


  • Rho family protein
  • hypoxia
  • mesenchymal stem cells
  • microRNAs
  • regenerative medicine


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