Psoralen synergizes with exosome-loaded SPC25 to alleviate senescence of nucleus pulposus cells in intervertebral disc degeneration

J Orthop Surg Res. 2023 Oct 24;18(1):622. doi: 10.1186/s13018-023-04085-w.

Abstract

Objective: To explore the mechanism of psoralen synergized with exosomes (exos)-loaded SPC25 on nucleus pulposus (NP) cell senescence in intervertebral disc degeneration (IVDD).

Methods: IVDD cellular models were established on NP cells by tert-butyl hydroperoxide (TBHP) induction, followed by the treatment of psoralen or/and exos from adipose-derived stem cells (ADSCs) transfected with SPC25 overexpression vector (ADSCs-oe-SPC25-Exos). The viability, cell cycle, apoptosis, and senescence of NP cells were examined, accompanied by the expression measurement of aggrecan, COL2A1, Bcl-2, Bax, CDK2, p16, and p21.

Results: After TBHP-induced NP cells were treated with psoralen or ADSCs-oe-SPC25-Exos, cell proliferation and the expression of aggrecan, COL2A1, Bcl-2, and CDK2 were promoted; however, the expression of Bax, p16, p21, and inflammatory factors was decreased, and cell senescence, cycle arrest, and apoptosis were inhibited. Of note, psoralen combined with ADSCs-oe-SPC25-Exos further decelerated NP cell senescence and cycle arrest compared to psoralen or ADSCs-oe-SPC25-Exos alone.

Conclusion: Combined treatment of psoralen and ADSCs-oe-SPC25-Exos exerted an alleviating effect on NP cell senescence, which may provide an insightful idea for IVDD treatment.

Keywords: Exosomes; Intervertebral disc degeneration; Nucleus pulposus; Psoralen; SPC25; Senescence.

MeSH terms

  • Aggrecans / metabolism
  • Exosomes* / metabolism
  • Ficusin / pharmacology
  • Humans
  • Intervertebral Disc Degeneration* / drug therapy
  • Intervertebral Disc Degeneration* / metabolism
  • Intervertebral Disc* / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / pharmacology
  • Nucleus Pulposus*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Aggrecans
  • Ficusin
  • bcl-2-Associated X Protein
  • SPC25 protein, human
  • Microtubule-Associated Proteins