Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing spondylitis

Abstract

BackgroundOne of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation. Previous studies have indicated that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of AS. The present study used a proteomic approach to identify novel AS-specific proteins by simultaneously comparing the expression profiles of synovial membranes from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA).MethodsSynovial tissues were collected from the hip joints of patients with AS and knee joints of patients with RA or OA (n = 10 for each disease) during joint replacement surgery. Proteins extracted from the synovial tissues were separated by 2-D electrophoresis (2-DE), and the proteins with significantly increased expression in the AS samples were subjected to MALDI-TOF/TOF-MS analysis. The results were verified using western blotting and immunohistochemistry. Levels of the candidate proteins in synovial fluids from knee joints (n = 40 for each disease) were measured using ELISA.ResultsThe proteomic approach revealed significantly increased expression of carbonic anhydrase I (CA1) in the synovial membrane of patients with AS as compared with the RA and OA tissue samples. Immunohistochemistry and western blotting analysis confirmed the findings described above. The ELISA detected a higher level of CA1 in synovial fluids from patients with AS than those with OA. The mean value of the CA1 level was also higher in AS patients as compared with RA patients. This study also detected increased expression of alpha-1-antitrypsin in the synovial tissues from AS patients, which is in agreement with other reports.ConclusionIn vitro experiments by other groups indicated that CA1 catalyzes the generation of HCO3- through the hydration of CO2, which then combines with Ca2+ to form a CaCO3 precipitate. Calcification is an essential step of bone formation. Substantial evidence indicates that carbonic anhydrase also stimulates bone resorption. Hence, overexpression of CA1 in the synovial tissues of AS patients may promote improper calcification and bone resorption in AS.

Overexpression of the transmembrane carbonic anhydrase isoforms IX and XII in the inflamed synovium

“…Data also indirectly point to low-pH-dependent reduction in the proliferation of lymphocytes and polymorphs, impaired chemotaxis and inhibition of antibody production 3 . Several forms of carbonic anhydrases (CAs, EC 4.2.1.1), metalloenzymes that reversibly catalyze the conversion of CO 2 to the bicarbonate ions and protons 4 , have been recognized in articular diseases, including CA I which is over-expressed in the synovium of the patients with ankylosing spondylitis 5 . Transgenic mice over-expressing CA I showed aggravated joint inflammation and destruction 6 .…”

Proteomic surveillance of putative new autoantigens in thyroid orbitopathy

“…Chang et al 23 investigated the levels of expression of CA1 by proteomic approach and suggested that CA1 may promote improper calcification and bone resorption in the synovium of patients with ankylosing spondylitis. In addition, the concentrations of CA1 and Zn in the red blood cell can be useful in estimating the extent of increased levels of thyroid hormone in patients with hyperthyroidism, and further distinguish patients with hyperthyroid GD from those with transient thyrotoxicosis 24…”

The role of carbonic anhydrase in the pathogenesis of vascular calcification in humans

“…In addition, the concentration of CA I in synovial fluids is higher in patients with ankylosing spondylitis than in patients with osteoarthritis and rheumatoid arthritis. These findings suggest that overexpression of CA I in the synovial tissues of ankylosing spondylitis patients may promote ectopic calcification [59]. In addition, the carbonic anhydrase inhibitor methazolamide has been used to treat active ankylosing spondylitis and it has been suggested that it may improve clinical symptoms by inhibiting carbonic anhydrase activity during the processes of bone resorption and new bone formation [60].…”