CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3β Pathway

This study investigates the role of the cannabinoid type 2 receptor (CB2R) in intervertebral disc degeneration (IVDD), a major cause of low back pain. The researchers explored how CB2R affects the senescence (aging) of nucleus pulposus cells (NPCs), which are crucial for disc health. The study used both a cell model induced by hydrogen peroxide (H2O2) to mimic NPC senescence and a rat model of IVDD caused by acupuncture. These models helped to understand the effects of CB2R activation on delaying NPC senescence and reducing IVDD. The research found that activating CB2R can delay NPC senescence, restore the balance of extracellular matrix (ECM) metabolism, and attenuate IVDD. The AMPK/GSK3β pathway was identified as a key factor in how CB2R regulates NPC senescence.

• 1
  CB2R expression is decreased in degenerated nucleus pulposus (NP) tissues from both human IVDD patients and rat acupuncture IVDD models, while the expression of p16INK4a increased.
• 2
  Activation of CB2R can significantly reduce the number of senescent cells, suppress the expression of senescence-associated secretory phenotype (SASP) factors like MMP9, MMP13, and HMGB1, and promote the expression of Col-2 and SOX9.
• 3
  The AMPK/GSK3β pathway plays a crucial role in CB2R regulation of NPC senescence. Inhibiting AMPK expression reversed the beneficial effects of CB2R activation, indicating that the AMPK/GSK3β pathway is involved in the mechanism by which CB2R regulates NPC senescence.