Background In rheumatoid arthritis (RA), the hypoxic environment of the synovium leads to the generation of lactic acid as synoviocytes switch glucose metabolism from an aerobic pyruvate pathway towards an anaerobic glycolytic pathway for metabolic energy production. Fibroblast-like synoviocytes (FLS) have an aggressive phenotype that leads to cartilage damage and bone destruction in RA. Acidification of the synovial environment has been associated with radiological joint destruction, activation of cathepsin B in synoviocytes and subsequent collagen degeneration, and in animal models has been associated with pathological joint damage. In a preliminary study we have demonstrated that human (FLS) express mRNA for the acid sensing proteins Accn3, Gpr4, Gpr68 and Trpv1. In this study we now demonstrate and describe the tissue localisation of these four acid sensing proteins in synovial biopsies from patients with RA.
Objectives To determine the tissue localisation of acid sensing proteins in synovium from patients with RA.
Methods Histochemical methods were used to study the expression of acid sensing proteins in arthroscopic biopsies from RA patients. Paraffin-embedded specimens (5 micron) were stained with rabbit polyclonal primary antibodies to Accn3, Gpr4, Gpr68 and Sections of human lung tissue, known to express Trpv1 and Gpr68, were used as a positive control.
Results Trpv1 was strongly expressed predominantly in synovial lining cells with a few positive cells localising around blood vessels. Gpr68 expression was highly restricted to the synovial lining, with few positive cells in deeper tissues. In contrast, Accn3 was distributed deeper within the synovium and around blood vessels but was absent from cells of the lining layer while Gpr4 was detected predominantly in adipose tissue.
Conclusions These data demonstrate that acid sensing proteins are present with distinct patterns of distribution in the synovium of RA patients. Trpv1 was the most strongly expressed and was found in all the patient tissues analysed. Interestingly, while three of the four proteins were largely confined to the synovial lining layer where the FLS reside, Accn3 was not detected in these cells. It is clear that other cells deeper within the synovial tissue also express acid sensing proteins. Further studies are currently underway to characterise the cell types in which they are expressed and to determine the functional significance of acid sensing proteins in the pathology of RA.
Disclosure of Interest None Declared