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The USP5-MATN3 axis in nucleus pulposus cell senescence: A deubiquitination mechanism protecting against

Chunyang Fan1, Jiechao Xia1, Yao Zhang1

  • 1Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital of Soochow University, Suzhou Medical College, Soochow University, Suzhou, China.

Cellular Signalling
|July 17, 2026
PubMed

Insights

Cellular senescence drives intervertebral disc degeneration (IVDD). The USP5/MATN3 pathway stabilizes MATN3, inhibiting senescence and slowing IVDD progression, offering new therapeutic targets for low back pain.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Orthopedics

Background:

  • Intervertebral disc degeneration (IVDD) is a primary cause of low back pain.
  • Cellular senescence in nucleus pulposus cells (NPCs) is a key factor in IVDD pathogenesis.
  • The upstream regulators of NPC senescence in IVDD are not fully understood.

Purpose of the Study:

  • To investigate the molecular mechanisms of IVDD.
  • To identify upstream regulators of cellular senescence in NPCs.
  • To explore potential therapeutic targets for IVDD.

Main Methods:

  • Protein expression analysis (MATN3).
  • In vitro NPC senescence assays.
  • In vivo rat tail puncture model for IVDD.
  • Immunoprecipitation-mass spectrometry and co-immunoprecipitation to identify protein interactions.
  • Ubiquitination and deubiquitination assays.

Main Results:

  • MATN3 protein levels significantly decreased in IVDD and correlated with NPC senescence.
  • Overexpression of MATN3 inhibited NPC senescence in vitro and delayed IVDD progression in vivo.
  • USP5 was identified as a direct interacting protein that stabilizes MATN3 via deubiquitination.
  • USP5 alleviated NPC senescence by upregulating MATN3.

Conclusions:

  • The USP5/MATN3 axis is a critical regulator of cellular senescence in NPCs.
  • This pathway plays a significant role in the progression of IVDD.
  • USP5 and MATN3 represent potential therapeutic targets for IVDD intervention.
Keywords:
Cellular senescenceDeubiquitinationIntervertebral disc degenerationUSP5/MATN3

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