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Sialoglycans modulate Siglec-5-TLR4 interactions in osteoarthritis.

Loise Råberg1, Fan Jia1, Ula von Mentzer1

  • 1Division of Chemical Biology, Department of Life Sciences, Chalmers University of Technology, 412 96 Gothenburg, Sweden.

Iscience
|December 8, 2025
PubMed
Summary

Osteoarthritis inflammation may be reduced by targeting the Siglec-5/Toll-like receptor 4 (TLR4) pathway. This interaction, influenced by sialylation, offers a potential strategy for joint preservation in osteoarthritis patients.

Keywords:
ImmunologyMolecular biology

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Area of Science:

  • Immunology
  • Biochemistry
  • Rheumatology

Background:

  • Osteoarthritis (OA) involves chronic inflammation, cartilage degradation, and joint pain.
  • Sialic acid-binding immunoglobulin-like lectin-5/14 (Siglec-5/14) was identified in OA synovial fluid.
  • The interaction between Siglec-5 and the proinflammatory receptor Toll-like receptor 4 (TLR4) was investigated.

Purpose of the Study:

  • To investigate the interaction between Siglec-5 and TLR4 in monocytes from OA patients.
  • To explore the role of sialylation patterns in OA inflammation.
  • To identify potential therapeutic targets for mitigating OA inflammation.

Main Methods:

  • Monocytes were stimulated with OA synovial fluid (OA SF), M-CSF, LPS, and sialidase.
  • Interleukin-6 (IL-6) production was measured.
  • Cellular phenotypes were assessed.
  • Siglec-5 and TLR4 colocalization was analyzed.

Main Results:

  • An inverse correlation between Siglec-5 and TLR4 suggests Siglec-5 suppresses inflammation.
  • OA SF-induced IL-6 production mirrored LPS- or sialidase-treated cells, indicating sialylation's role.
  • Siglec-5 and TLR4 demonstrated a time- and sialoglycan-dependent direct interaction.

Conclusions:

  • A Siglec-5-TLR4 axis modulated by sialylation was identified in OA.
  • This axis represents a potential therapeutic strategy for reducing inflammation and preserving joint integrity in OA.