Assoc.Prof. Mag. Dr. Stefan Tögel
MedUni Vienna RESEARCHER OF THE MONTH, April 2017
The award-winning study by Stefan Toegel and coworkers revealed that Galectin-1 serves as coordinator of degenerative processes in osteoarthritic chondrocytes by stimulating NFκB-mediated inflammation. Using immunohistochemistry in samples of articular knee cartilage from osteoarthritis patients, the authors found significant correlation of Galectin-1 expression with the histopathological degree of cartilage degeneration. In cell culture, Galectin-1 binds to the cell surface of osteoarthritic chondrocytes via a glycan-dependent mechanism and significantly upregulates the expression of enzymes involved in matrix degradation. Genome-wide analysis indicated the induction of an inflammatory gene signature centrally involving NFκB signalling, as also confirmed using targeted inhibition assays. Upcoming work by the group will focus on the upstream mechanisms of Galectin-1 activity in osteoarthritic cartilage and on clarifying the roles of other galectins in this process. Ultimately it is the aim to identify novel therapeutic targets for osteoarthritis.
Selected literature
1. Toegel S, Weinmann D, André S, Walzer SM, Bilban M, Schmidt S, Chiari C, Windhager R, Krall C, Bennani Baiti IM, Gabius H-J: Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB-Regulated Gene Network. J Immunol 2016, 196:1910–1921.
2. Osório J: Osteoarthritis: Galectin-1 damages cartilage via inflammation. Nat Rev Rheumatol 2016, 12:132–133.
3. Toegel S, Harrer N, Plattner VE, Unger FM, Viernstein H, Goldring MB, Gabor F, Wirth M: Lectin binding studies on C-28/I2 and T/C-28a2 chondrocytes provide a basis for new tissue engineering and drug delivery perspectives in cartilage research. Journal of Controlled Release 2007, 117:121–129.
4. Toegel S, Plattner VE, Wu SQ, Goldring MB, Chiari C, Kolb A, Unger FM, Nehrer S, Gabor F, Viernstein H, Wirth M: Lectin binding patterns reflect the phenotypic status of in vitro chondrocyte models. In Vitro Cell Dev Biol-Animal 2009, 45:351–360.
5. Toegel S, Pabst M, Wu SQ, Grass J, Goldring MB, Chiari C, Kolb A, Altmann F, Viernstein H, Unger FM: Phenotype-related differential alpha-2,6- or alpha-2,3-sialylation of glycoprotein N-glycans in human chondrocytes. Osteoarthr Cartilage 2010, 18:240–248.
6. Pabst M, Wu SQ, Grass J, Kolb A, Chiari C, Viernstein H, Unger FM, Altmann F, Toegel S: IL-1beta and TNF-alpha alter the glycophenotype of primary human chondrocytes in vitro. Carbohydr Res 2010, 345:1389–1393.
7. Pabst M, Grass J, Toegel S, Liebminger E, Strasser R, Altmann F: Isomeric analysis of oligomannosidic N-glycans and their dolichol-linked precursors. Glycobiology 2012, 22:389–399.
8. Toegel S, Bieder D, André S, Altmann F, Walzer SM, Kaltner H, Hofstaetter JG, Windhager R, Gabius H-J: Glycophenotyping of osteoarthritic cartilage and chondrocytes by RT-qPCR, mass spectrometry, histochemistry with plant/human lectins and lectin localization with a glycoprotein. Arthritis Res Ther 2013, 15:R147.
9. Toegel S, Bieder D, André S, Kayser K, Walzer SM, Hobusch G, Windhager R, Gabius H-J: Human osteoarthritic knee cartilage: fingerprinting of adhesion/growth-regulatory galectins in vitro and in situ indicates differential upregulation in severe degeneration. Histochem Cell Biol 2014, 142:373–388.
10. Weinmann D, Schlangen K, André S, Schmidt S, Walzer SM, Kubista B, Windhager R, Toegel S, Gabius H-J: Galectin-3 Induces a Pro-degradative/inflammatory Gene Signature in Human Chondrocytes, Teaming Up with Galectin-1 in Osteoarthritis Pathogenesis. Sci Rep, 2016, 6: 39112. http://doi.org/10.1038/srep39112
11. Kaltner H, Toegel S, Caballero GG, Manning JC, Ledeen RW, Gabius H-J: Galectins: their network and roles in immunity/tumor growth control. Histochem Cell Biol, 2017: 147:239–256.