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YY1/miR-140-5p/Jagged1/Notch axis mediates cartilage progenitor/stem cells fate reprogramming in knee osteoarthritis

Yang Chen1, Guangneng Liao2, Ting Ma3

  • 1Department of Orthopedic Surgery & Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.

International Immunopharmacology
|June 9, 2023
PubMed

Insights

This study reveals a new pathway involving YY1, miR-140-5p, and Jagged1/Notch signaling that controls cartilage stem cell changes in osteoarthritis. Targeting this axis may offer new osteoarthritis treatments.

Area of Science:

  • Regenerative Medicine
  • Molecular Biology
  • Osteoarthritis Pathogenesis

Background:

  • Osteoarthritis (OA) involves cartilage degeneration, with cartilage progenitor/stem cells (CPCs) crucial for repair.
  • Regulatory mechanisms governing CPC fate in OA remain largely unknown.
  • MicroRNA-140-5p (miR-140-5p) has emerged as a potential protector of CPCs in OA.

Purpose of the Study:

  • To elucidate the upstream regulators and downstream effectors of miR-140-5p in OA CPC fate reprogramming.
  • To investigate the role of the transcription factor Ying Yang 1 (YY1) and the Jagged1/Notch signaling pathway in OA CPCs.

Main Methods:

  • Luciferase reporter assays to identify miR-140-5p targets.
  • Loss- and gain-of-function experiments in human CPCs.
  • Validation of molecular mechanisms in a rat OA model.

Main Results:

  • miR-140-5p directly targets Jagged1, inhibiting Notch signaling in human CPCs.
  • miR-140-5p promotes healthy CPC fate, an effect reversed by Jagged1.
  • Increased YY1 represses miR-140-5p and enhances Jagged1/Notch signaling, contributing to OA progression.

Conclusions:

  • A novel YY1/miR-140-5p/Jagged1/Notch signaling axis regulates OA CPC fate reprogramming.
  • YY1 and Jagged1/Notch signaling promote OA, while miR-140-5p offers protection.
  • This axis presents potential therapeutic targets for osteoarthritis.
Keywords:
Cartilage progenitor/stem cellsFate reprogrammingJagged1OsteoarthritisYing Yang 1microRNA-140-5p

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