Work

Sialoglycans modulate Siglec-5-TLR4 interactions in osteoarthritis

Year: 2025

Type: article

Abstract: Osteoarthritis (OA) is characterized by chronic, low-grade inflammation that contributes to cartilage degradation and joint pain. We previously identified sialic acid-binding immunoglobulin-like lectin-5/14 (Siglec-5/14) in synovial fluid of OA patients (OA SF), which prompted us to investigate its interaction with the sialylated proinflammatory receptor Toll-like receptor 4 (TLR4) in monocytes. Here, we reveal an inverse correlation between Siglec-5 and TLR4, suggesting that Siglec-5 may suppress inflammation. To gain mechanistic insights, monocytes stimulated with OA SFs were compared to macrophage colony stimulating factor (M-CSF), lipopolysaccharide (LPS), and sialidase, to assess patient-specific inflammatory pathways and phenotypes. Notably, OA SF that triggered elevated interleukin (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 preserving joint integrity in OA.

Source: iScience

DOI: 10.1016/j.isci.2025.113979

Authors: Loise Råberg, Fan Jia, Ula von Mentzer, Vignesh Venkatakrishnan, Niclas G. Karlsson, Alexandra Stubelius

Institutions: Chalmers University of Technology, OsloMet – Oslo Metropolitan University

Language: English

Topic: Glycosylation and Glycoproteins Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240