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CircRUNX2 through has-miR-203 regulates RUNX2 to prevent osteoporosis

Qudong Yin1, Jian Wang1, Qiang Fu2

  • 1Department of Orthopaedics, Wuxi No. 9 People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China.

Journal of Cellular and Molecular Medicine
|October 17, 2018
PubMed
Abstract

Insights

Circular RNA circRUNX2 inhibits miR-203, enhancing RUNX2 expression and promoting osteogenic differentiation. This finding suggests circRUNX2 as a potential therapeutic target for preventing osteoporosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Osteoporosis is a significant skeletal disorder characterized by decreased bone density and increased fracture risk.
  • Understanding the molecular mechanisms regulating osteogenic differentiation is crucial for developing effective osteoporosis treatments.

Purpose of the Study:

  • To elucidate the molecular mechanism of circRUNX2 in osteogenic differentiation.
  • To investigate the regulatory interactions between circRUNX2, miR-203, and RUNX2 in bone metabolism.

Main Methods:

  • Expression analysis of circRUNX2, miR-203, and RUNX2 in clinical samples and human bone mesenchymal stem cells (hBMSCs).
  • Quantitative real-time PCR (qRT-PCR) and Western blotting to assess RNA and protein levels.
  • Biotin pull-down, RNA immunoprecipitation (RIP), RNA fluorescence in situ hybridization (FISH), and Dual-Luciferase Reporter assays to determine molecular interactions.
  • Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining to evaluate osteogenic differentiation.

Main Results:

  • CircRUNX2 expression was found to be downregulated in bone tissues of osteoporotic patients.
  • CircRUNX2 acts as a molecular sponge for miR-203, inhibiting its expression.
  • MiR-203 targets the 3'-untranslated region (3'-UTR) of RUNX2, downregulating its expression and inhibiting osteogenic differentiation.
  • Overexpression of circRUNX2 promoted osteogenic differentiation markers (RUNX2, OCN, OPN, BSP) and prevented osteoporosis.

Conclusions:

  • CircRUNX2 sponges miR-203, leading to enhanced RUNX2 expression and promoting osteogenic differentiation.
  • CircRUNX2 plays a protective role against osteoporosis.
  • CircRUNX2 represents a potential novel therapeutic target for osteoporosis treatment.
Keywords:
MiR-203RUNX2circRUNX2osteoporosis

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