AB0735 ALTERED GALECTIN EXPRESSION CORRELATE WITH TNF-MEDIATED INFLAMMATORY CARTILAGE DAMAGE
Authors: S. Hayer, B. Niederreiter, C. Strauß, R. Windhager, D. Aletaha, S. Toegel
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Galectins (Gal) are a family of soluble ß-galactoside-binding proteins that serve as regulators in multiple physiological processes like proliferation or cell adhesion. There is growing evidence that galectins are up-regulated in synovial tissue and sera from patients with RA.1-4 However, the role of galectins in inflammatory bone erosions and cartilage breakdown has not been elucidated in RA, limiting mechanistic insights into their precise function. <h3>Objectives:</h3> Thus, the present study investigates the galectin profile in inflammatory joint damage in a TNF-driven arthritis mouse model. <h3>Methods:</h3> Articular joints from 10-week old human tumor necrosis factor transgenic mice (hTNFtg, Tg197 strain), with established chronic inflammatory, erosive arthritis model, and from age-matched wild-type (wt) littermates were investigated for the expression of Gal-1, -2, -3, -4, -7, -8 and -9 in tissue extracts and sections. Areas of galectin expression in different compartments of inflamed joints were quantitatively assessed using TissueQuest software. Severity of synovitis, bone erosions and cartilage damage was determined in TRAP and SafO-stained sections and their linkage to individual galectins was calculated by Spearman correlation analysis. <h3>Results:</h3> In general, an increased expression of galectin was found in various knee joint compartments such as synovial tissue and menisci of hTNFtg mice compared to wt mice. Progressive joint inflammation led to cartilage damage indicated by complete proteoglycan loss, partial cartilage erosions of the deeper, calcified zone and invasion of the inflammatory synovial pannus tissue. Interestingly, immunohistochemical stainings revealed an increased expression of Gal-1, -4, -7 and -8, but not of Gal-2, -3 and -9 in cartilage from hTNFtg mice compared to healthy cartilage from wt animals. These findings were observed particularly in tibial rather than femoral cartilage. Whereas most galectins were found to be exclusively expressed in chondrocytes, Gal-1, -4 and -7 overexpression was also apparent in cartilage matrix of hTNFtg mice. Furthermore, correlation analysis revealed a significant linkage between increased galectin-1, -4, -7, -8 expression and progression of cartilage erosion. In contrast, Gal-9 was found to be downregulated upon damage. <h3>Conclusion:</h3> Under TNF-driven inflammatory conditions, a distinct pattern of glycan-binding galectins is notable in articular cartilage. The change in galectin pattern is linked to the progression of cartilage erosion, which suggests a functional role of galectins in the pathophysiology of inflammatory cartilage damage. <h3>REFERENCES:</h3> [1] Mendez-Huergo, S. P. et al. Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differential Regulation and Correlation With Disease Activity. Front Immunol 9, 3057, doi:10.3389/fimmu.2018.03057 (2018). [2] Nielsen, M. A. et al. Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis. Scand J Rheumatol 52, 33-41, doi:10.1080/03009742.2021.1992860 (2023). [3] Vilar, K. M. et al. Galectin-1, -4, and -7 Were Associated with High Activity of Disease in Patients with Rheumatoid Arthritis. Autoimmune Dis 2019, 3081621, doi:10.1155/2019/3081621 (2019). [4] Nielsen, M. A. et al. Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Naïve Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts. Cells 12, doi:10.3390/cells12020327 (2023). <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>