Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through MALAT1/ miR-138-5p/SLC7A11 Coexpression Regulation

ACS Biomater Sci Eng. 2024 Aug 12;10(8):4839-4854. doi: 10.1021/acsbiomaterials.3c01944. Epub 2024 Jul 30.

Abstract

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

Keywords: MALAT1; SLC7A11; extracellular vesicles; intervertebral disc degeneration; miR-138-5p.

MeSH terms

  • Animals
  • Extracellular Vesicles* / genetics
  • Extracellular Vesicles* / metabolism
  • Ferroptosis / genetics
  • Gene Expression Regulation
  • Humans
  • Intervertebral Disc Degeneration* / genetics
  • Intervertebral Disc Degeneration* / metabolism
  • Intervertebral Disc Degeneration* / pathology
  • Intervertebral Disc Degeneration* / therapy
  • Male
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nucleus Pulposus / metabolism
  • Nucleus Pulposus / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Umbilical Cord / cytology
  • Umbilical Cord / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • MALAT1 long non-coding RNA, human
  • MIRN138 microRNA, human