Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-62508
Frommer, Klaus W; Schäffler, Andreas; Büchler, Christa; Steinmeyer, Jürgen; Rickert, Markus; Rehart, Stefan; Brentano, Fabia; Gay, Steffen; Müller-Ladner, Ulf; Neumann, Elena (2012). Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis? Annals of the Rheumatic Diseases, 71(10):1724-1732.
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:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine|
04 Faculty of Medicine > Center for Integrative Human Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||04 Jun 2012 10:59|
|Last Modified:||25 Nov 2012 21:43|
|Publisher:||BMJ Publishing Group|
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