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

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 o...

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Published in:Histochemistry & Cell Biology Vol. 157; no. 2; pp. 139 - 152
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: pictorial research tables/charts Journal Article
Published: Springer Nature Feb2022
Online Access:View this record in EBSCOhost
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      dt: Feb2022
      vid: 157
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00418-021-02053-1
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        atl: Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro.
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          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
        affil: Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
      sug:
        subj:
          Proteins
          Osteoarthritis
          Genes
          Chondrocytes
          Carbohydrates
          Interleukin 1
          Matrix Metalloproteinases
          Peptide Hydrolases
          Reverse Transcriptase Polymerase Chain Reaction Methods
          RNA, Messenger
          Gene Expression Profiling
          Phosphorylation
          NF-kappa B
          Glycoproteins
      ab: 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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