Universität zu Köln

Zeinert, Isabel ORCID: 0000-0001-5790-7306, Schmidt, Luisa ORCID: 0000-0002-9805-4941, Baar, Till ORCID: 0000-0002-6744-1463, Gatto, Giulio, De Giuseppe, Anna, Korb-Pap, Adelheid ORCID: 0000-0002-0106-903X, Pap, Thomas, Mahabir, Esther ORCID: 0000-0002-9573-5127, Zaucke, Frank ORCID: 0000-0002-7680-9354, Brachvogel, Bent ORCID: 0000-0002-3923-0554, Krüger, Marcus ORCID: 0000-0002-5846-6941, Krieg, Thomas ORCID: 0000-0001-5616-8476 and Eckes, Beate ORCID: 0000-0002-0936-0702 (2025). Matrix-mediated activation of murine fibroblast-like synoviocytes. Experimental Cell Research, 445 (1). pp. 1-13. Elsevier. ISSN 0014-4827

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Abstract

[Artikel-Nr. 114408] Fibroblast-like synoviocytes (FLS) are key cells promoting cartilage damage and bone loss in rheumatoid arthritis (RA). They are activated to assume an invasive and migratory phenotype. While mechanisms of FLS activation are unknown, evidence suggests that pre-damaged extracellular matrix (ECM) of the cartilage can trigger FLS activation. Integrin α11β1 might be involved in the activation, as it is increased in RA patients and hTNFtg mice, an RA mouse model. We treated murine chondrocytes with TNFα to produce a damaged, RA-like matrix. Comparison to healthy chondrocyte matrix revealed decreased ECM proteins, e.g. collagens and proteoglycans, increased matrix- degrading proteins and elevated levels of inflammatory cytokines. FLS responded to the damaged chondrocyte matrix with a matrix-remodeling and pro-inflammatory pheno- type characterized by a gene signature involved in matrix degradation and increased production of CLL11 and CCL19. Damaged chondrocyte matrix stimulated increased Itga11 expression in FLS, correlating with the increased α11β1 amounts in RA patients. FLS deficient in integrin α11β1 released lower amounts of inflammation-associated cytokines. Our results demonstrate differences in healthy and RA-like chondrocyte ECM and distinctly different responses of wt FLS to damaged versus healthy ECM.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Zeinert, Isabel UNSPECIFIED https://orcid.org/0000-0001-5790-7306 UNSPECIFIED Schmidt, Luisa UNSPECIFIED https://orcid.org/0000-0002-9805-4941 UNSPECIFIED Baar, Till UNSPECIFIED https://orcid.org/0000-0002-6744-1463 UNSPECIFIED Gatto, Giulio UNSPECIFIED UNSPECIFIED UNSPECIFIED De Giuseppe, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Korb-Pap, Adelheid UNSPECIFIED https://orcid.org/0000-0002-0106-903X UNSPECIFIED Pap, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Mahabir, Esther UNSPECIFIED https://orcid.org/0000-0002-9573-5127 UNSPECIFIED Zaucke, Frank UNSPECIFIED https://orcid.org/0000-0002-7680-9354 UNSPECIFIED Brachvogel, Bent UNSPECIFIED https://orcid.org/0000-0002-3923-0554 UNSPECIFIED Krüger, Marcus UNSPECIFIED https://orcid.org/0000-0002-5846-6941 UNSPECIFIED Krieg, Thomas UNSPECIFIED https://orcid.org/0000-0001-5616-8476 UNSPECIFIED Eckes, Beate UNSPECIFIED https://orcid.org/0000-0002-0936-0702 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-797164
Identification Number:	10.1016/j.yexcr.2025.114408
Journal or Publication Title:	Experimental Cell Research
Volume:	445
Number:	1
Page Range:	pp. 1-13
Number of Pages:	1
Date:	February 2025
Publisher:	Elsevier
ISSN:	0014-4827
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Faculty of Medicine > Medizinische Statistik und Bioinformatik > Institut für Medizinische Statistik und Bioinformatik � IMSB Faculty of Medicine > Weitere > Translationale Genomik Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79716