Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?
Annals of Rheumatic Diseases, 05/16/2012
Frommer KW et al. – The results clearly suggest a pro–inflammatory and joint–destructive role of all adiponectin isoforms in rheumatoid arthritis (RA) pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.Methods
- Affymetrix microarrays were used to screen for changes in gene expression of rheumatoid arthritis synovial fibroblasts (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.
- 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.