Open Access

Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells

  • Authors:
    • Hao Zhang
    • Di Zhang
    • Hui Wang
    • Yilei Liu
    • Wenyuan Ding
    • Guangpu Fan
    • Xianzhong Meng
  • View Affiliations

  • Published online on: March 4, 2025     https://doi.org/10.3892/mmr.2025.13481
  • Article Number: 116
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) and heme oxygenase 1 (HO‑1) attenuate intervertebral disc degeneration (IVDD). However, whether BMSC‑derived exosomes attenuate IVDD by delivering HO‑1 to nucleus pulposus (NP) cells remains to be elucidated. Mouse BMSCs were characterized by multilineage differentiation and surface marker molecule detection. Exosomes Exo and Exo‑HO‑1 were isolated from BMSCs and HO‑1‑overexpressing BMSCs by ultracentrifugation and characterized by observing their morphology, detecting the exosome marker proteins, tumor susceptibility gene 101 (TSG101) and CD63 and analyzing their particle size. Interleukin‑1 β (IL‑1β)‑stimulated NP cells were used as the IVDD cell model. The influence of Exo or Exo‑HO‑1 on IL‑1β‑urged apoptosis and senescence in NP cells was determined by flow cytometry, western blotting and senescence‑associated β‑galactosidase (SA‑β‑gal) staining. Exo and Exo‑HO‑1 did not vary in size or morphology. Exo‑HO‑1 markedly repressed IL‑1β‑prompted apoptosis in NP cells, accompanied with a prominent increase in Cleaved caspase 3 and Bax protein levels and a marked decrease in Bcl‑2 protein levels. Exo and Exo‑HO‑1 both decreased the number of SA‑β‑gal‑positive NP cells and arrested NP cells in the G1 phase. Exo‑HO‑1 had stronger effects than Exo, suggesting that Exo‑HO‑1 can weaken IL‑1β‑induced NP cell senescence. In addition, Exo and Exo‑HO‑1 repressed IL‑1β mediating the phosphorylation of p65 and nuclear translocation of p65. In conclusion, HO‑1‑overexpressing BMSC‑derived exosomes blocked the nuclear factor‑kappa B signaling in IL‑1β‑stimulated NP cells, thus impairing cell apoptosis and senescence.
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May-2025
Volume 31 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang H, Zhang D, Wang H, Liu Y, Ding W, Fan G and Meng X: Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells. Mol Med Rep 31: 116, 2025.
APA
Zhang, H., Zhang, D., Wang, H., Liu, Y., Ding, W., Fan, G., & Meng, X. (2025). Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells. Molecular Medicine Reports, 31, 116. https://doi.org/10.3892/mmr.2025.13481
MLA
Zhang, H., Zhang, D., Wang, H., Liu, Y., Ding, W., Fan, G., Meng, X."Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells". Molecular Medicine Reports 31.5 (2025): 116.
Chicago
Zhang, H., Zhang, D., Wang, H., Liu, Y., Ding, W., Fan, G., Meng, X."Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells". Molecular Medicine Reports 31, no. 5 (2025): 116. https://doi.org/10.3892/mmr.2025.13481
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