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microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1

Gang Liu1, Feng-Li Chen2, Feng Ji1

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

Oncotarget
|February 9, 2018
PubMed

Insights

MicroRNA-19a protects human osteoblasts from dexamethasone by targeting TSC1 to activate mTORC1 signaling. This pathway also enhances Nrf2 activity, reducing oxidative stress and improving osteoblast survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Activation of mTOR complex 1 (mTORC1) shows potential in protecting human osteoblasts from dexamethasone-induced damage.
  • Tuberous sclerosis complex 1 (TSC1) acts as an upstream inhibitor of mTORC1.

Purpose of the Study:

  • To investigate the role of microRNA-19a (miR-19a) in regulating TSC1 and its impact on osteoblast protection against dexamethasone.
  • To elucidate the signaling pathways involved in miR-19a-mediated cytoprotection.

Main Methods:

  • Utilized OB-6 osteoblastic cells and primary human osteoblasts.
  • Assessed the effect of miR-19a on TSC1 mRNA and protein levels.
  • Investigated the impact of miR-19a on mTORC1 activation using RAD001 and Raptor shRNA.
  • Examined the role of TSC1 knockdown via shRNA.
  • Analyzed mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and reactive oxygen species (ROS) production.

Main Results:

  • miR-19a was found to target the 3' untranslated regions of TSC1 mRNA, leading to its downregulation in osteoblasts.
  • Overexpression of miR-19a activated mTORC1 and conferred protection against dexamethasone.
  • Inhibition of mTORC1 or knockdown of TSC1 mimicked the protective effects of miR-19a.
  • miR-19a activated mTORC1-dependent Nrf2 signaling and reduced dexamethasone-induced ROS production.

Conclusions:

  • miR-19a protects human osteoblasts from dexamethasone by downregulating TSC1 and activating the TSC1-mTORC1 signaling pathway.
  • The protective mechanism involves the activation of Nrf2 signaling and subsequent reduction of oxidative stress.
Keywords:
dexamethasonemTOR complex 1 (mTORC1)microRNA-19aosteoblaststuberous sclerosis complex 1 (TSC1)

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