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

• Published in: Histochemistry and cell biology 2022-02, Vol.157 (2), p.139-151
• Main Authors: Pichler, Katharina M., Fischer, Anita, Alphonsus, Jürgen, Chiari, Catharina, Schmidt, Sebastian, Kenn, Michael, Schreiner, Wolfgang, Weinmann, Daniela, Rothbauer, Mario, Windhager, Reinhard, Gabius, Hans‑Joachim, Toegel, Stefan
• Format: Article
• Language: English
• Subjects: Arthritis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cartilage diseases; Cell Biology; Cells, Cultured; Chondrocytes; Chondrocytes - chemistry; Chondrocytes - metabolism; Chondrocytes - pathology; Collagenase 3; Developmental Biology; Galactose; Galectin 4 - genetics; Galectin 4 - metabolism; Humans; IL-1β; Inflammation; Matrix metalloproteinase; Metalloproteinase; NF-κB protein; Original Paper; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Phosphorylation; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sulfatide; Transcriptomes
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-021-02053-1

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-1β (IL-1β) 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-κB 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.