Overexpression of LMP-1 Decreases Apoptosis in Human Nucleus Pulposus Cells via Suppressing the NF- κ B Signaling Pathway

Oxid Med Cell Longev. 2020 Dec 13:2020:8189706. doi: 10.1155/2020/8189706. eCollection 2020.

Abstract

Intervertebral disc degeneration (IDD) is a prevalent disease characterized by low back pain. Increasing extracellular matrix (ECM) synthesis and decreasing nucleus pulposus cell (NPC) apoptosis are promising strategies to recover degenerated NP. LIM mineralization protein- (LMP-) 1 has anti-inflammatory potential and is a promising gene target for the treatment of NP degeneration. In this study, we measured the expression of LMP-1 in the NP of patients. Then, we constructed LMP-1-overexpressing NPCs using lentiviral vectors and investigated the effects of LMP-1 on cell proliferation, apoptosis, and ECM synthesis in NPCs. The results showed that LMP-1 was highly expressed in the NP of patients. LMP-1 overexpression significantly increased proliferation and decreased apoptosis in NPCs. The expression of collagen II and sulfated glycosaminoglycan (sGAG) in NPCs was also upregulated after LMP-1 was overexpressed. Moreover, we demonstrated that LMP-1 decreased apoptosis of NPCs by inhibiting NF-κB signaling activation. These findings suggest that LMP-1 plays an essential role in mediating apoptosis in NPCs by regulating NF-κB signaling and can be used as a gene target for the treatment of IDD.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis*
  • Adult
  • Animals
  • Apoptosis*
  • Cell Proliferation
  • Collagen / metabolism
  • Cytoskeletal Proteins / biosynthesis*
  • Extracellular Matrix / metabolism
  • Glycosaminoglycans / metabolism
  • Humans
  • Intervertebral Disc Degeneration / metabolism*
  • LIM Domain Proteins / biosynthesis*
  • Lentivirus
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Nucleus Pulposus / metabolism*
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Glycosaminoglycans
  • LIM Domain Proteins
  • NF-kappa B
  • PDLIM7 protein, human
  • RNA, Small Interfering
  • Collagen