Background The calcium-sensing receptor's (CaSR) expression is ubiquitous in the body but depends on cell type and extracellular conditions such as inflammation. It has been previously demonstrated that human circulating monocytes express the CaSR. However, data on the physiological roles of CaSR expression in monocytes are still sparse. The investigation of CaSR expression in monocytes in different clinical situations is therefore required. The objectives of the present study were to study CaSR expression in monocytes in different type of rheumatisms.
Objectives Given the influence of pro-inflammatory cytokines on CaSR expression, we assessed CaSR expression in monocytes isolated from synovial fluid of patients with different types of rheumatisms (osteoarthritis versus inflammatory rheumatisms) and explored whether CaSR expression could differ depending on the type of rheumatisms and whether the nature of synovial fluid could influence the in vitro expression of CaSR.
Methods In this pilot, cross-sectional study, we included all patients who presented with an articular effusion in the rheumatology department. Surface and total CaSR expressions in monocytes isolated from synovial fluid and blood were assessed by flow cytometry analysis. U937 cells (human monocyte cell line) were cultured for 24 hours in presence of cell-free synovial fluids in order to specify the influence of different synovial fluids on CaSR expression in vitro.
Results Forty one patients were included: osteoarthritis (OA) (n=10), microcristallin rheumatisms (n=10), rheumatoid arthritis (RA) (n=12) and other inflammatory rheumatisms (n=9). In monocytes isolated from synovial fluid, the measure of CaSR expression (surface and total) shows that local pathological conditions influence CaSR expression. Indeed, CaSR expression was increased in OA compared to the 3 other groups with inflammatory rheumatisms (microcristallin or auto-immune). We also observed a significant difference between the microcristallin rheumatism group and the RA group, with a lower expression in the RA group. Accordingly, CaSR expression in monocytes isolated from peripheral blood of the same patients was significantly increased in OA patients compared to RA. However, in circulating monocytes no other significant difference were observed between groups, suggesting that CaSR expression in monocytes isolated from synovial fluid could be a marker of interest in rheumatic diseases. Moreover, CaSR expression was increased in vitro when U937 cells were incubated with synovial fluid from OA patients. This effect was significantly lowered when “inflammatory” synovial fluids were used.
Conclusions Our results indicate that CaSR expression in monocytes isolated from synovial fluid is higher in osteoarthritis than in inflammatory rheumatisms and that CaSR expression is modulated by extracellular conditions, notably the nature of the synovial fluid. Given the role played by monocytes in the pathogenesis of chronic rheumatisms, monocytes could be interesting therapeutic targets via the CaSR.
Acknowledgements Flow cytometry analysis was performed at the plateforme d'Imagerie Cellulaire et d'Analyse des Protéines (ICAP), Université de Picardie Jules Verne, Amiens, France.
Disclosure of Interest None declared