miR-21-5p and canonical Wnt signaling pathway promote osteoblast function through a feed-forward loop induced by fluoride

Toxicology. 2022 Jan 30:466:153079. doi: 10.1016/j.tox.2021.153079. Epub 2021 Dec 20.

Abstract

Long-term excessive exposure to fluoride from environmental sources can cause serious public health problems such as dental fluorosis and skeletal fluorosis. The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis and canonical Wnt signaling pathway participate in the progress. However, the specific mechanism that how canonical Wnt signaling pathway was mediated is not yet clear. In this study, we found that miR-21-5p induced the activation of canonical Wnt signaling pathway via targeting PTEN and DKK2 during fluoride induced osteoblasts activation and firstly demonstrated the forward loop between canonical Wnt signaling and miR-21-5p in the process. These findings suggested an important regulatory role of miR-21-5p on canonical Wnt signaling pathway during skeletal fluorosis and miR-21-5p might be a potential therapeutic target for skeletal fluorosis.

Keywords: Canonical Wnt signaling pathway; MiR-21-5p; Osteoblast activation; SaoS2; Skeletal fluorosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Diseases, Metabolic / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Fluorides / toxicity*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / metabolism*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • PTEN Phosphohydrolase / metabolism*
  • Wnt Signaling Pathway*

Substances

  • DKK2 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Fluorides