Bergapten alleviates osteoarthritis by regulating the ANP32A/ATM signaling pathway

FEBS Open Bio. 2019 Jun;9(6):1144-1152. doi: 10.1002/2211-5463.12648. Epub 2019 May 23.

Abstract

Osteoarthritis (OA) is a chronic degenerative disease that commonly affects the elderly. Current drug therapies for treating OA may cause adverse side effects, and so there remains a need to develop alternative treatments. Bergapten (BG) is a coumarin phytohormone that is widely found in fruits and has antioxidative and anti-inflammatory effects. Here, we tested the hypothesis that BG may restrict the progression of OA by examining its effect on OA chondrocytes. We observed that BG significantly ameliorated interleukin (IL)-1β-induced expression of inflammatory cytokines and mediators, including interleukin 1 (Il-1), interleukin 6 (Il-6), tumor necrosis factor α (Tnf-α), cyclooxygenase 2 (Cox-2) and matrix metalloproteinase 13 (Mmp-13), maintained chondrocyte phenotype, and promoted the secretion of cartilage-specific extracellular matrix. We provide evidence that BG exerts its anti-inflammatory effect by activating the ANP32A/ATM signaling pathway, which was recently verified to be associated with OA. In conclusion, these findings indicate that BG may be a potential candidate for treatment of OA.

Keywords: ANP32A/ATM signal; IL-1β; bergapten; chondrocytes; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methoxypsoralen / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chondrocytes / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Ficus / chemistry
  • Inflammation / drug therapy
  • Knee Joint / cytology
  • Matrix Metalloproteinase 13 / metabolism
  • Nuclear Proteins / metabolism*
  • Osteoarthritis / metabolism*
  • Plant Extracts / pharmacology*
  • Plant Growth Regulators / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • Anp32a protein, rat
  • Anti-Inflammatory Agents
  • Cytokines
  • Nuclear Proteins
  • Plant Extracts
  • Plant Growth Regulators
  • 5-Methoxypsoralen
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Ataxia Telangiectasia Mutated Proteins
  • Matrix Metalloproteinase 13