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Extended report
Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?
  1. Klaus W Frommer1,
  2. Andreas Schäffler2,
  3. Christa Büchler2,
  4. Jürgen Steinmeyer3,
  5. Markus Rickert4,
  6. Stefan Rehart5,
  7. Fabia Brentano6,
  8. Steffen Gay6,
  9. Ulf Müller-Ladner1,
  10. Elena Neumann1
  1. 1Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff-Klinik, Bad Nauheim, Germany
  2. 2Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
  3. 3Department of Orthopedics and Experimental Orthopedics, University Hospital Giessen and Marburg, Giessen, Germany
  4. 4Justus-Liebig-University of Giessen, Orthopedics and Orthopedic Surgery, Giessen, Germany
  5. 5Department of Orthopedics and Trauma Surgery, St Markus Hospital, Frankfurt, Germany
  6. 6Center for Experimental Rheumatology, University Hospital Zürich, Zürich, Switzerland
  1. Correspondence to Elena Neumann, Department of Internal Medicine and Rheumatology Justus-Liebig-University Giessen Kerckhoff-Klinik Benekestrasse 2-8 D-61231 Bad Nauheim, Germany; e.neumann{at}kerckhoff-klinik.de

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.

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Footnotes

  • Funding This work was supported by the German research society (NE1174/3-1), the FP 6 Autocure, FP7 Masterswitch and IAR Epalinges.

  • Ethics approval All specimens were obtained with the approval of the Ethics Committee of the Justus-Liebig-University of Giessen.

  • Patient consent Obtained.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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