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


Journal

Histochemistry and cell biology
ISSN: 1432-119X
Titre abrégé: Histochem Cell Biol
Pays: Germany
ID NLM: 9506663

Informations de publication

Date de publication:
Feb 2022
Historique:
accepted: 08 11 2021
pubmed: 1 12 2021
medline: 15 3 2022
entrez: 30 11 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34846578
doi: 10.1007/s00418-021-02053-1
pii: 10.1007/s00418-021-02053-1
pmc: PMC8847242
doi:

Substances chimiques

Galectin 4 0
RNA, Messenger 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

139-151

Informations de copyright

© 2021. The Author(s).

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Auteurs

Katharina M Pichler (KM)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Anita Fischer (A)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Jürgen Alphonsus (J)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Catharina Chiari (C)

Department of Orthopedics and Trauma Surgery, Division of Orthopedics, Medical University of Vienna, 1090, Vienna, Austria.

Sebastian Schmidt (S)

Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, 80539, Munich, Germany.

Michael Kenn (M)

Center for Medical Statistics, Informatics and Intelligent Systems, Institute of Biosimulation and Bioinformatics, Medical University of Vienna, Vienna, Austria.

Wolfgang Schreiner (W)

Center for Medical Statistics, Informatics and Intelligent Systems, Institute of Biosimulation and Bioinformatics, Medical University of Vienna, Vienna, Austria.

Daniela Weinmann (D)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Mario Rothbauer (M)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Reinhard Windhager (R)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Department of Orthopedics and Trauma Surgery, Division of Orthopedics, Medical University of Vienna, 1090, Vienna, Austria.

Hans-Joachim Gabius (HJ)

Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, 80539, Munich, Germany.

Stefan Toegel (S)

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. stefan.toegel@muv.ac.at.
Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria. stefan.toegel@muv.ac.at.

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Classifications MeSH