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MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone

Sai Zhao1, Li Mao2, Shou-Guo Wang3

  • 1Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.

Oncotarget
|December 30, 2017
PubMed

Insights

MicroRNA-200a activates the antioxidant Nrf2 pathway by targeting Keap1, protecting human osteoblasts from dexamethasone-induced oxidative stress and cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Dexamethasone treatment causes oxidative stress and injury in human osteoblasts.
  • NF-E2-related factor 2 (Nrf2) is a crucial signaling pathway for antioxidant defense.
  • Keap1 is a negative regulator of Nrf2.

Purpose of the Study:

  • To investigate the potential of microRNA-mediated Keap1 silencing to activate Nrf2 signaling.
  • To determine if microRNA-200a can protect human osteoblasts from dexamethasone-induced damage.

Main Methods:

  • Utilized OB-6 osteoblastic cells and primary human osteoblasts.
  • Employed microRNA-200a mimics and anti-sense oligonucleotides.
  • Used Keap1 shRNA for gene silencing.
  • Assessed reactive oxygen species (ROS) production and apoptosis.
  • Analyzed miR-200a and Keap1 levels in necrotic femoral head tissues.

Main Results:

  • MicroRNA-200a (miR-200a) depletion of Keap1 led to Nrf2 stabilization in OB-6 cells.
  • miR-200a activated Nrf2 signaling, inhibiting dexamethasone-induced ROS production and apoptosis.
  • Keap1 silencing via shRNA or miR-200a protected primary human osteoblasts from dexamethasone.
  • Decreased miR-200a levels correlated with increased Keap1 mRNA in necrotic femoral head tissues.

Conclusions:

  • miR-200a activates the Nrf2 antioxidant pathway by suppressing Keap1.
  • miR-200a protects human osteoblasts from dexamethasone-induced oxidative stress and cell death.
  • This pathway represents a potential therapeutic target for conditions involving osteoblast injury.
Keywords:
Nrf2dexamethasonekeap1miR-200aosteoblasts

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