AQUAPORIN EXPRESSION IN THE SYNOVIAL TISSUES OF PATIENTS WITH OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS

Background: Aquaporins (AQPs) are usually present at the plasma membrane, where they regulate the influx and outflow of water and small molecules. They are important for the regulation of water homoeostasis in cells and organisms. An analysis of AQP molecular mechanisms in synovial tissues may suggest new treatments for hydrarthrosis. Objectives: To determine whether AQPs are expressed in the synovial tissues of patients with OA and RA, and to examine the patterns of expression in patients with and without hydrarthrosis. Methods: Synovial tissue samples were obtained from patients with OA and with RA. AQPs mRNA were detected in synovial tissue samples from patients with OA and RA using RT–PCR. Fibroblast-like synoviocytes (FLSs) from patients with OA and RA were cultured and stimulated with TNF-α. The expression of AQPs in FLSs was examined using RT–PCR and western blot analyses and the function of aquaglyceroporin was examined by a glycerol uptake assay. Results: The presence of AQP1, AQP3, AQP7 and AQP9 mRNAs was confirmed in all of the synovial tissue samples from OA and RA patients. The expression levels of AQP9 were significantly higher in RA samples than in OA samples (P < 0.01). AQP9 expression was significantly higher in synovial tissues from the OA patients with hydrarthrosis than in those without (P < 0.05). AQP1 and AQP3 mRNA expression levels were not affected by TNF-α treatment. AQP9 mRNA and protein expression were strongly induced with TNF-α treatment in FLSs, whereas AQP1 and -3 mRNA expression levels were not affected by TNF-α treatment. [³H] glycerol uptake was significantly higher in OA FLSs treated with TNF-α. Conclusions: This study showed that AQP1, AQP3 and AQP9 were expressed in synovia from OA and RA patients. The synovial tissues of patients with OA with hydrarthrosis significantly expressed more AQP9s than without hydrarthrosis. AQP9 expression was strongly induced in FLSs with TNF-α. AQP9 might be related to the pathogenesis of hydrarthrosis and inflammatory synovitis. The therapy focusing on AQP9-mediated water transport would be a new approach to hydrarthrosis. References: 1.Nozaki K, Ishii D, Ishibashi K. Intracellular aquaporins: clues for intracellular water transport? Pflugers Arch 2008; 456:701–7. 2.Verkman AS. Aquaporin water channels and endothelial cell function. J Anat 2002;200:617–27. 3.Magni F, Sarto C, Ticozzi D et al. Proteomic knowledge of human aquaporins. Proteomics 2006;6:5637–49. 4.Tsukaguchi H, Weremowicz S, Morton CC et al. Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol Renal Physiol 1999;277:685–96. 5.Nagahara M, Waguri-Nagaya Y, T Yamagami, Aoyama M, Tada T, Inoue K. Asai K, Otsuka T. TNF-a induced aquaporin 9 in synoviocytes from patients with OA and RA. Rheumatol 2010;49 :898-906. Disclosure of Interest: None DeclaredCitation: , volume 72, supplement s3, year 2013, page Session: Poster session Thursday ( )