Heme Oxygenase 1‑overexpressing Bone Marrow Mesenchymal Stem Cell‑derived Exosomes Suppress Interleukin‑1 Beta‑induced Apoptosis and Aging of Nucleus Pulposus Cells

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2025 Mar 7

PMID 40052562

Authors

Hao Zhang

Di Zhang

Hui Wang

Yilei Liu

Wenyuan Ding

Guangpu Fan

Xianzhong Meng

Affiliations

Soon will be listed here.

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 G 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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