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microRNA-214-3p Suppresses Ankylosing Spondylitis Fibroblast Osteogenesis via BMP-TGFβ Axis and BMP2

Lixiang Ding1, Yukun Yin2, Yu Hou1

  • 1Department of Spine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Frontiers in Endocrinology
|May 3, 2021
PubMed

Insights

MicroRNA-214-3p is downregulated in ankylosing spondylitis (AS) fibroblasts, promoting osteogenesis. Restoring miR-214-3p levels inhibits this process by targeting BMP2 and the BMP-TGFβ axis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Rheumatology

Background:

  • Ankylosing spondylitis (AS) is an inflammatory rheumatic disease.
  • MicroRNAs (miRs) play a role in fibroblast osteogenesis in AS.
  • The specific mechanism of miR-214-3p in AS osteogenic differentiation requires clarification.

Purpose of the Study:

  • To investigate the role and mechanism of miR-214-3p in the osteogenic differentiation of fibroblasts from patients with ankylosing spondylitis (AS).
  • To assess the relationship between miR-214-3p, bone morphogenic protein 2 (BMP2), and the BMP-TGFβ axis in AS fibroblast osteogenesis.

Main Methods:

  • Fibroblast isolation from AS and femoral neck fracture patient ligaments.
  • Osteogenic induction and identification of cultured fibroblasts.
  • Gain- and loss-of-function experiments for miR-214-3p and BMP2.
  • Alizarin red S staining and alkaline phosphatase (ALP) activity assays.
  • Measurement of miR-214-3p, BMP2, and related protein levels.

Main Results:

  • miR-214-3p was significantly downregulated in AS fibroblasts.
  • Downregulation of miR-214-3p correlated with enhanced ALP activity and calcium nodule formation.
  • Overexpression of miR-214-3p reversed the enhanced osteogenic activity.
  • BMP2 was identified as a direct target of miR-214-3p.
  • miR-214-3p inhibited AS fibroblast osteogenesis by targeting BMP2 and suppressing the BMP-TGFβ axis.

Conclusions:

  • miR-214-3p acts as a negative regulator of osteogenic differentiation in AS fibroblasts.
  • The miR-214-3p/BMP2/BMP-TGFβ axis is a critical pathway in AS fibroblast osteogenesis.
  • Targeting miR-214-3p may offer a novel therapeutic strategy for ankylosing spondylitis.
Keywords:
BMP–TGFβ signaling pathwayankylosing spondylitisbone morphogenic protein 2microRNA-214-3posteogenic differentiation

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