Title:Exosomes derived from Mouse Bone Marrow Mesenchymal Stem
Cells Attenuate Nucleus Pulposus Cell Apoptosis via the miR-155-
5p/Trim32 Axis
Volume: 24
Issue: 8
Author(s): Fei Chen, Shangze Li, Ji Wu, Qunfeng Guo, Haibin Wang, Bin Ni*Jun Yang*
Affiliation:
- Department of Orthopaedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003,
China
- Department of Orthopaedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003,
China
Keywords:
Intervertebral disc degeneration, miRNA, cell death, exosomes, mesenchymal stem cells, Trim32.
Abstract:
Background: Lower back pain, shown to be strongly associated with IVDD,
affects approximately 60%–80% of adults and has a considerable societal and economic
impact. Evidence suggests that IVDD, caused by abnormal apoptosis of nucleus
pulposus cells (NPCs), can be treated using MSC-derived exosomes.
Objective: This study aimed to evaluate the role of miR155-5p/Trim32 in intervertebral
disc disease (IVDD) and elucidate the underlying molecular mechanisms. Deregulating
miR-155 has been shown to promote Fas-mediated apoptosis in human IVDD. Evidence
also suggests that tripartite motif (TRIM)-containing protein 32 (Trim32) is regulated by
miR-155. However, the role of miR155-5p/Trim32 in IVDD remains unclear.
Methods: Cell viability was checked using CCK-8 kits, and flow cytometry was used to
analyze cell cycle and apoptosis. Cell migration was measured with a Transwell assay,
while a luciferase assay was adopted to study how miR-155-5p interacts with Trim32.
The roles of Trim32 and miR-155-5p were studied by silencing or up-regulating them in
NPCs, while qPCR and immunoblots were used to evaluate mRNA and protein changes,
respectively.
Results: TNF-α treatment significantly inhibited cell viability but promoted Trim32
expression in primary mouse NPCs. Administration of bone marrow mesenchymal stem
cells (BMSCs) attenuated primary NPC cell cycle arrest and apoptosis induced by TNF-
α. BMSCs-derived exosomes could be taken up by NPCs to inhibit TNF-α-induced cell
cycle arrest and apoptosis through miR-155-5p. Examination of the underlying
mechanism showed that miR-155-5p targeted Trim32. Moreover, Trim32 overexpression
inhibited the effect of BMSCs-derived exosomes on primary mouse NPC cell apoptosis
induced by TNF-α.
Conclusion: Overall, these findings suggest that exosomes from BMSCs can suppress
TNF-α-induced cell cycle arrest and apoptosis in primary mouse NPCs through the
delivery of miR-155-5p by targeting Trim32. This study provides a promising therapeutic
strategy for IVDD.
