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Author Spotlight: Treating Knee Osteoarthritis with Tuina - A New Perspective
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ROR2 blockade as a therapy for osteoarthritis.

Anne-Sophie Thorup1, Danielle Strachan2, Sara Caxaria2

  • 1William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. asthorup@gmail.com fdellaccio@gmail.com.

Science Translational Medicine
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Summary

Blocking receptor tyrosine kinase-like orphan receptor 2 (ROR2) shows promise for treating osteoarthritis. This approach improves cartilage health and reduces pain by inhibiting yes-associated protein (YAP) signaling, offering a potential new therapy.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Orthopedics

Background:

  • Osteoarthritis (OA) involves articular cartilage loss, bone remodeling, pain, and disability.
  • Current pharmacological treatments cannot halt OA progression.
  • Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is implicated in OA pathogenesis.

Purpose of the Study:

  • To investigate the role of ROR2 in osteoarthritis.
  • To evaluate the therapeutic potential of blocking ROR2 signaling in OA models.
  • To elucidate the downstream signaling pathways affected by ROR2 in OA.

Main Methods:

  • Studied ROR2 expression in response to inflammatory cytokines and mechanical stress.
  • Utilized in vitro cell culture models (C3H10T1/2 cells, human articular chondrocytes).
  • Employed mouse models of instability-induced osteoarthritis and evaluated ROR2 silencing effects.

Main Results:

  • ROR2 was upregulated in OA cartilage; its ligand WNT5A and downstream targets YAP and CTGF were also elevated in human OA.
  • ROR2 blockade promoted chondrogenic differentiation and suppressed cartilage-degrading enzymes (ADAMTS-4, ADAMTS-5) in vitro.
  • ROR2 silencing in mice improved structural outcomes, reduced pain, and showed no toxicity; human chondrocyte studies indicated conserved anabolic effects.

Conclusions:

  • Blocking ROR2 inhibits YAP signaling, improving cartilage integrity and pain in OA models.
  • ROR2 blockade demonstrates efficacy and tolerability in preclinical OA models.
  • ROR2 inhibition represents a promising therapeutic strategy for osteoarthritis with potential human applications.