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

Xiaotian Chang,Jinxiang Han,Xinfeng Yan,Yazhou Cui,Shui Sun,Yan Zhao

doi:10.1186/1471-2474-11-279

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.

Highlights

One of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation
Using MALDI-TOF MS, the spots with increased expression in AS synovial tissues were identified as carbonic anhydrase I (CA1) and alpha-1-antitrypsin precursor (A1AT)
By comparing the expression profiles of AS synovial membranes with those of OA, 11 protein spots were detected with more than 3-fold greater expression. These proteins were identified as Ig gamma1 chain C region, dynein heavy chain, fibrinogen gamma chain precursor, catalase, SH3 and multiple ankyrin repeat domains protein 2, haptoglobin precursor, DNAdependent protein kinase catalytic subunit, apolipoprotein A-I precursor, serotransferrin precursor, microtubule-actin crosslinking factor 1 isoform 4, and intersectin 1. These proteins were expressed at increased levels in the synovial tissues of rheumatoid arthritis (RA) patients or in the synovial tissues of OA patients, and they were not expressed at significantly increased levels in the synovial tissues of AS patients

Summary

Introduction

One of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation. 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). Ankylosing spondylitis (AS) is a chronic inflammatory disease that can cause significant complications by affecting the sacroiliac joints and axial skeleton. AS is characterized by two key pathologic features: sacroiliac joint and spinal inflammation and new bone formation studies revealed that pathological changes in the synovium of patients with AS are closely related to disease progression. Proteomics is a powerful new tool for rheumatology research Using this approach, Liu et al demonstrated high expression of the haptoglobin precursor in the sera of patients with AS [5].

Methods

Results

Discussion

Conclusion