Abstract
BackgroundThe dysfunction of articular chondrocytes is a crucial step in rheumatoid arthritis (RA) pathogenesis while its molecular mechanisms are not fully known. This study was aimed to investigate the expression of aquaporin 4 (AQP4) in articular chondrocytes of adjuvant-induced arthritis (AIA) rats and its involvement in AIA development.MethodsThirty rats were divided into normal and AIA group (n = 15). Rat AIA was induced by intradermal injection of complete Freund’s adjuvant and evaluated by secondary paw swelling and histological assessments on knee joint damage. Localization and protein expression of AQP4 in articular cartilage were examined by immunohistochemistry and western blot. In vitro study, AIA articular chondrocytes were cultured and treated with acetazolamide, an AQPs inhibitor. AQP4 protein level, cell proliferation and mRNA levels of type-II collagen (COII) and aggrecan were measured by western blot, MTT assay and real-time PCR, respectively.ResultsThe results of immunohistochemistry and western blot indicated that AQP4 showed higher protein levels in cartilage tissues of AIA rats than that of normal rats. Correlation analysis revealed that AQP4 protein level in cartilage tissues of AIA rats remarkably correlated positively with secondary paw swelling on day 26 after AIA induction as well as pathological scores on joint damage. Additionally, acetazolamide treatment effectively decreased AQP4 protein level, increased cell proliferation and mRNA levels of COII and aggrecan, suggesting AQP4 inhibition by acetazolamide could normalize the dysfunction of AIA articular chondrocytes in vitro.ConclusionsOur data provide certain experimental evidence that AQP4 over-expression in articular chondrocytes aggravated AIA severity and might be a novel target for RA treatment.
Highlights
The dysfunction of articular chondrocytes is a crucial step in rheumatoid arthritis (RA) pathogenesis while its molecular mechanisms are not fully known
adjuvant-induced arthritis (AIA) rats exhibited an apparent swelling of non-injected hind paws, which was termed as secondary inflammation (Fig. 1b)
We found that aquaporin 4 (AQP4) protein levels in cartilage tissues from AIA rats were significantly elevated as compared with normal rats
Summary
The dysfunction of articular chondrocytes is a crucial step in rheumatoid arthritis (RA) pathogenesis while its molecular mechanisms are not fully known. This study was aimed to investigate the expression of aquaporin 4 (AQP4) in articular chondrocytes of adjuvant-induced arthritis (AIA) rats and its involvement in AIA development. In the affected joints of RA, multiple extracellular pathological changes such as hydrarthrosis, acidosis and hyperosmotic stress induce the dysfunction of articular chondrocytes, e.g., excessive apoptosis and reduced ECM synthesis ability, eventually lead to articular cartilage destruction [8]. It is well known that AQP4 possess very high single channel water permeability (3fold greater than that of AQP1) [18], while previous studies of AQP4 mainly aim at nervous system diseases [19]. The potential pathological role of AQP4 in RA cartilage damage is still unknown
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