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The protective role of CD44 and microRNA-146a in tendinopathy

Che-Chia Hsu1, Shih-Yao Chen2,3, Po-Yen Ko1

  • 1Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Bone & Joint Research
|January 23, 2026
PubMed
Abstract

Insights

The CD44-AKT-miR-146a signaling axis protects against tendinopathy by reducing apoptosis in tenocytes and tendons. This pathway mitigates cell death by suppressing Smad4 expression, offering a potential therapeutic target for tendinopathy.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Cellular Biology

Background:

  • Tendinopathy involves pain and dysfunction due to inflammation, senescence, and apoptosis.
  • Blocking CD44 signaling worsens apoptosis and inflammation in tendinopathic tenocytes.
  • MicroRNA-146a (miR-146a) counters IL-1β-induced senescence and is upregulated by CD44.

Purpose of the Study:

  • Investigate the CD44-miR-146a signaling axis in regulating apoptosis in tendinopathy.
  • Elucidate the role of CD44 and miR-146a in tendinopathic cell death.
  • Explore potential therapeutic strategies targeting this pathway.

Main Methods:

  • Overexpressed CD44 and miR-146a using lentiviral vectors in rat tenocytes and tendons.
  • Assessed apoptosis via TUNEL staining.
  • Utilized PI3K/AKT inhibitor and CD44 antibody to dissect the CD44-AKT-miR-146a pathway.
  • Examined Smad4 expression using in situ hybridization and immunohistochemistry.

Main Results:

  • Overexpression of CD44 and miR-146a significantly reduced apoptosis in tendinopathic tenocytes.
  • The CD44-AKT-miR-146a axis mitigated apoptosis in IL-1β-stimulated tenocytes and an Achilles tendinopathy rat model.
  • This protective effect was primarily achieved by suppressing Smad4 expression.

Conclusions:

  • The CD44-AKT-miR-146a axis plays a protective role in tendinopathy.
  • Modulating this pathway effectively reduces apoptosis in tendinopathic cells and tissues.
  • Targeting the AKT/miR-146a/Smad4 pathway offers a promising therapeutic approach for tendinopathy.

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