Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro

Pichler, Katharina M.; Fischer, Anita; Alphonsus, Jürgen; Chiari, Catharina; Schmidt, Sebastian; Kenn, Michael; Schreiner, Wolfgang; Weinmann, Daniela; Rothbauer, Mario; Windhager, Reinhard; Gabius, Hans-Joachim und Toegel, Stefan (2021): Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro. In: Histochemistry and Cell Biology, Bd. 157, Nr. 2: S. 139-151

Abstract

Galectin-4 (Gal-4) is a member of the galectin family, which have been identified as galactose-binding proteins. Gal-4 possesses two tandem repeat carbohydrate recognition domains and acts as a cross-linking bridge in sulfatide-dependent glycoprotein routing. We herein document its upregulation in osteoarthritis (OA) in correlation with the extent of cartilage degradation in vivo. Primary human OA chondrocytes in vitro respond to carbohydrate-inhibitable Gal-4 binding with the upregulation of pro-degradative/-inflammatory proteins such as interleukin-1 beta (IL-1 beta) and matrix metalloproteinase-13 (MMP-13), as documented by RT-qPCR-based mRNA profiling and transcriptome data processing. Activation of p65 by phosphorylation of Ser536 within the NF-kappa B pathway and the effect of three p65 inhibitors on Gal-4 activity support downstream involvement of such signaling. In 3D (pellet) cultures, Gal-4 presence causes morphological and biochemical signs of degradation. Taken together, our findings strongly support the concept of galectins acting as a network in OA pathogenesis and suggest that blocking their activity in disease progression may become clinically relevant in the future.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin > Veterinärwissenschaftliches Department
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0948-6143
• Sprache: Englisch