title: Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine and Rheumatology Justus-Liebig-University Giessen Kerckhoff-Klinik Benekestrasse 2-8 D-61231 Bad Nauheim, Germany.
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Frommer
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäffler
authors.forename: Christa
authors.initials: C
authors.lastname: Büchler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Steinmeyer
authors.forename: Markus
authors.initials: M
authors.lastname: Rickert
authors.forename: Stefan
authors.initials: S
authors.lastname: Rehart
authors.forename: Fabia
authors.initials: F
authors.lastname: Brentano
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
mesh_terms: D052242:Adiponectin / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D052242:Adiponectin; D018925:Chemokines; D020033:Protein Isoforms