Effect of galectin-3 on synovial inflammation in knee osteoarthritis via stimulating phosphatidylinositol-3-kinase/Akt pathway
Issued Date
2023-09-01
Resource Type
ISSN
15675769
eISSN
18781705
Scopus ID
2-s2.0-85165567946
Pubmed ID
37481852
Journal Title
International Immunopharmacology
Volume
122
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Immunopharmacology Vol.122 (2023)
Suggested Citation
Udomsinprasert W., Ungsudechachai T., Wunthong S., Yuttanarad S., Jittikoon J., Honsawek S. Effect of galectin-3 on synovial inflammation in knee osteoarthritis via stimulating phosphatidylinositol-3-kinase/Akt pathway. International Immunopharmacology Vol.122 (2023). doi:10.1016/j.intimp.2023.110673 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88172
Title
Effect of galectin-3 on synovial inflammation in knee osteoarthritis via stimulating phosphatidylinositol-3-kinase/Akt pathway
Author's Affiliation
Other Contributor(s)
Abstract
Galectin-3 (Gal-3), a glycan-binding protein responsible for inflammation, has been reportedly implicated in inflammatory arthritis. This study aimed to determine clinical and pathological effects of Gal-3 on inflammation in knee osteoarthritis (OA). Gal-3 mRNA and protein levels in synoviocytes, synovium, synovial fluid, and plasma of knee OA patients were determined using real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Signaling mechanism underlying inflammatory effect of Gal-3 was further elucidated in human knee OA synoviocytes. Clinical study uncovered significant increases in plasma and synovial fluid Gal-3 levels in knee OA patients, particularly those with advanced-stage. In knee OA patients, plasma Gal-3 was significantly associated with radiographic severity and indicators of body composition, physical performance, and knee pain and disability. In the inflamed synovium of knee OA patients, further analysis depicted a marked up-regulation of Gal-3 mRNA expression, consistent with immunohistochemical analysis showing localization of Gal-3 protein in the lining and sublining layers of the inflamed synovium. An in vitro study unveiled that aberrant Gal-3 mRNA expression was regulated by tumor necrosis factor (TNF)-α in knee OA synoviocytes. Gal-3 significantly enhanced production of NO and IL-6, up-regulated mRNA expressions of IL-6, NF-κB, and MMP-13, and down-regulated mRNA expressions of ACAN and SOX-9 via stimulating Akt phosphorylation in knee OA synoviocytes. Gal-3 exerted an inflammatory action, which might emerge as a possible mediator of synovitis and cartilage degeneration in knee OA.