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bioRxiv · 10.1101/2025.03.18.643878

Sialoglycans modulate Siglec-5 - TLR4 Interactions in Osteoarthritis

Raberg, L.·Jia, F.·von Mentzer, U.·Karlsson, N. G.·Stubelius, A.
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Abstract

Osteoarthritis (OA) is characterized by chronic, low-grade inflammation that contributes to cartilage degradation and joint pain. We previously identified Siglec-5/14 in synovial fluid of OA patients (OA SF), which prompted us to investigate its interaction with the sialylated proinflammatory receptor TLR4 in monocytes. Here, we reveal an inverse correlation between Siglec-5 and TLR4, suggesting Siglec-5 may suppress inflammation. To gain mechanistic insights, monocytes stimulated with OA SFs were compared to M-CSF, LPS, and sialidase, to assess patient-specific inflammatory pathways and phenotypes. Notably, OA SF that triggered elevated IL-6 production in monocytes exhibited phenotypes similar to those of LPS- or sialidase-treated cells, reinforcing the role of sialylation patterns influencing OA severity. To confirm direct interaction of Siglec-5 and TLR4, colocalization was analyzed, displaying a time- and sialoglycan-dependent interaction. These findings reveal a Siglec-5-TLR4 axis modulated by sialylation, highlighting a potential strategy for mitigating inflammation and preserve joint integrity in OA.

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Raberg, L., Jia, F., von Mentzer, U., Karlsson, N. G., Stubelius, A.. 2025-03-19. Sialoglycans modulate Siglec-5 - TLR4 Interactions in Osteoarthritis. https://doi.org/10.1101/2025.03.18.643878

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