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Echinococcus granulosus promotes MAPK pathway-mediated osteoclast differentiation by inhibiting Nrf2 in osseous

Yaqing Liu1,2, Jing Li1, Zhendong Zhang1

  • 1The First Affiliated Hospital of Shihezi University, Xinjiang Uygur Autonomous Region, Shihezi, 832000, China.

Veterinary Research
|April 12, 2025
PubMed

Insights

Echinococcus granulosus infection causes bone loss by inhibiting Nrf2, which normally prevents osteoclast over-differentiation. Restoring Nrf2 function could treat osseous echinococcosis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pathology

Background:

  • Osseous echinococcosis, caused by Echinococcus granulosus, leads to significant bone destruction.
  • Osteolytic changes are driven by excessive osteoclast differentiation at infection sites.
  • Nrf2 is a critical regulator of osteoclast formation and function.

Purpose of the Study:

  • To investigate the regulatory role of Nrf2 in osteoclast differentiation during Echinococcus granulosus infection.
  • To elucidate the mechanism by which Nrf2 influences bone resorption in osseous echinococcosis.

Main Methods:

  • In vitro studies using bone marrow mononuclear cells (BMMCs) treated with protoscoleces (PSC).
  • Nrf2 knockdown and activation experiments.
  • In vivo studies using a murine model of osseous cystic echinococcosis (CE) and Nrf2 knockout mice.
  • Analysis of intracellular reactive oxygen species (ROS) and MAPK pathway phosphorylation.

Main Results:

  • PSC intervention suppressed Nrf2 and heme oxygenase-1 (HO-1) expression, increased ROS, and promoted osteoclast differentiation.
  • Nrf2 knockdown enhanced osteoclast formation, while Nrf2 activation inhibited it.
  • Nrf2 knockout mice exhibited more severe bone destruction and osteoclast activity in vivo.
  • MAPK pathway phosphorylation was increased after PSC intervention.

Conclusions:

  • Echinococcus granulosus infection inhibits Nrf2 expression, leading to increased osteoclast differentiation and bone resorption.
  • Nrf2 plays a crucial role in regulating bone destruction in osseous echinococcosis.
  • Nrf2 represents a potential molecular target for therapeutic interventions against osseous echinococcosis.
Keywords:
Echinococcus granulosusNrf2osseous cystic echinococcosisosteoclasts

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