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Hyperbaric oxygen treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human

Chi-Chien Niu1, Song-Shu Lin, Li-Jen Yuan

  • 1Department of Orthopaedic Surgery, Hyperbaric Oxygen Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
|August 14, 2012
PubMed

Insights

Hyperbaric oxygen (HBO) therapy can protect degenerating human intervertebral disc cells by reducing inflammation and apoptosis. This study shows HBO suppresses harmful cell signaling pathways, promoting cell survival and matrix production.

Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Orthopedics

Background:

  • Degenerating intervertebral discs exhibit increased catabolic and inflammatory factors like interleukin-1 (IL-1) and nitric oxide (NO).
  • Elevated nitric oxide (NO) levels are linked to apoptosis in degenerating disc cells, contributing to disc degeneration.
  • Understanding cellular responses to treatments like hyperbaric oxygen (HBO) is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the effects of hyperbaric oxygen (HBO) on degenerated human nucleus pulposus cells (NPCs).
  • To elucidate the molecular mechanisms underlying HBO's impact on cellular signaling, inflammation, and apoptosis in NPCs.
  • To evaluate HBO's potential to modulate key pathways involved in disc degeneration.

Main Methods:

  • Human nucleus pulposus cells (NPCs) were exposed to hyperbaric oxygen (100% O2 at 2.5 ATA).
  • Analyzed MAPK pathway activation (ERK1/2, JNK, p38) using phosphor-kinase arrays.
  • Quantified IL-1β and NO levels via ELISA, aggrecan and type II collagen gene expression via real-time PCR, and apoptosis-related proteins (Bcl-2, Bax, caspases) via Western blotting.

Main Results:

  • HBO treatment significantly reduced IL-1β expression and nitric oxide (NO) synthesis in NPCs.
  • Suppressed phosphorylation of key MAPK pathway components (ERK1/2, JNK, p38) was observed.
  • HBO increased aggrecan and type II collagen gene expression, while up-regulating the Bcl-2/Bax ratio and inhibiting caspase 3 and 9 activity, indicating reduced mitochondrial apoptosis.

Conclusions:

  • Hyperbaric oxygen (HBO) treatment effectively suppresses pro-inflammatory and catabolic factors in degenerated human NPCs.
  • HBO mitigates apoptosis in degenerated disc cells by inhibiting the MAPK signaling and mitochondrial apoptotic pathways.
  • These findings suggest HBO is a promising therapeutic approach for intervertebral disc degeneration.

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