Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?

Frommer, Klaus W. and Schaeffler, Andreas and Buechler, Christa and Steinmeyer, Juergen and Rickert, Markus and Rehart, Stefan and Brentano, Fabia and Gay, Steffen and Mueller-Ladner, Ulf and Neumann, Elena (2012) Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis? ANNALS OF THE RHEUMATIC DISEASES, 71 (10). pp. 1724-1732. ISSN 0003-4967,

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Abstract

Objectives Several clinical studies have suggested the adipocytokine adiponectin is involved in the progression of rheumatoid arthritis (RA). From this point of view, adiponectin might present a new therapeutic target. However, as adiponectin also exerts beneficial effects in the human organism, a strategy that would allow its detrimental effects to be abolished while maintaining the positive effects would be highly favourable. To elucidate such a strategy, the authors analysed whether the different adiponectin isoforms induce diverging effects, especially with regard to rheumatoid arthritis synovial fibroblasts (RASF), a central cell type in RA pathogenesis capable of invading into and destroying cartilage. Methods Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay. Results In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes. Conclusion The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.

Item Type: Article
Uncontrolled Keywords: HIGH-MOLECULAR-WEIGHT; VASCULAR ENDOTHELIAL-CELLS; COMPLEMENT-RELATED PROTEIN; KAPPA-B ACTIVATION; SYNOVIAL FIBROBLASTS; GLOBULAR ADIPONECTIN; ADIPOSE-TISSUE; BONE-FORMATION; GENE-TRANSFER; MICE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2020 04:57
Last Modified: 06 May 2020 04:57
URI: https://pred.uni-regensburg.de/id/eprint/18068

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