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RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

Hao Ding1,2, Xiaoliang Mei3,2, Lintao Li1

  • 1Department of Orthopedics, Jinling Hospital, Jinling Clinical Medical College of Nanjing Medical University, Nanjing 211166, China.

Molecules and Cells
|January 10, 2023
PubMed

Insights

Leucine-rich repeat containing 15 (LRRC15) drives rheumatoid arthritis (RA) progression by increasing inflammation and joint damage. Suppressing LRRC15 via RUNX1 offers a potential therapeutic strategy for RA.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Leucine-rich repeat containing 15 (LRRC15) is linked to osteoarthritis but its role in rheumatoid arthritis (RA) is unclear.
  • Understanding LRRC15's function and regulatory mechanisms in RA is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the role of LRRC15 in RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) mouse models.
  • To elucidate the epigenetic mechanisms regulating LRRC15 expression in RA.

Main Methods:

  • Analysis of LRRC15 expression in human RA synovial tissues.
  • In vitro studies using RA-FLS to assess LRRC15's functional impact.
  • In vivo studies using CIA mice to evaluate LRRC15 inhibition effects.
  • Investigation of the RUNX1-CBF-β pathway in regulating LRRC15 transcription.

Main Results:

  • LRRC15 was overexpressed in RA synovial tissues, correlating with enhanced RA-FLS proliferation, migration, invasion, and angiogenesis.
  • LRRC15 overexpression accelerated pro-inflammatory cytokine release.
  • LRRC15 knockdown inhibited synovial proliferation and reduced bone destruction in CIA mice.
  • RUNX1 was found to transcriptionally repress LRRC15 via binding to CBF-β.
  • RUNX1 overexpression inhibited RA-FLS invasiveness and pro-inflammatory cytokine expression, effects reversed by LRRC15 overexpression or RUNX1-CBF-β interaction inhibition.

Conclusions:

  • RUNX1-mediated repression of LRRC15 plays a protective role in RA development.
  • Targeting the RUNX1-LRRC15 pathway presents a potential therapeutic avenue for RA.
Keywords:
LRRC15RUNX1epigeneticfibroblast-like synoviocytesrheumatoid arthritis

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