Background Osteoclast-associated receptor [OSCAR] is expressed by monocyte, endothelial and dendritic cells. OSCAR is a co-stimulation receptor involved in transducing immunoreceptor tyrosine-based activation (ITAM) signals for differentiation from monocytes into active osteoclasts (OCs). Endothelial OSCAR expression may induce monocyte adhesion increasing monocyte extravasation available for osteoclastogenesis in affected joints. Higher expression of OSCAR by endothelial and pre-OCs, as detected by immunohistochemistry, is present in active RA compared with OA and healthy synovial samples (Crotti ART 2012). Inflammation in RA may increase OSCAR expression as supported by increased monocyte (Herman ART 2012) and endothelial cell (Crotti ART 2012) OSCAR expression in response to TNF-alpha in vitro. OSCAR expression in early RA (less than 6 months post diagnosis) and cartilage pannus junction (CPJ) and non-CPJ samples from established RA has not been reported.
Objectives To examine OSCAR expression in the synovium of early RA patients at diagnosis and 6 months following treatment. OSCAR was also assessed in the CPJ and non-CPJ tissues of patients with established RA.
Methods Samples included synovial biopsies from 15 patients newly diagnosed for RA at 0 and 6 months. CPJ and non-CPJ samples from established RA joints were also assessed (n=14). Serial sections for both cohorts were stained for OSCAR, TRAP (to identify pre-OCs/OCs) and von Willebrand factor (to identify vessels). Positive cells were counted (TRAP) or scored semiquantitatively (OSCAR) in 6x 2mm2 fields. A paired T test was used to detect significance.
Results OSCAR was associated with the synovial lining cells and distributed sparsely in association with monocytes in the subsynovial tissue or lymphoid aggregates in both early and established RA. A subset of samples from both cohorts showed a very mild staining associated with the vasculature and lumen. In early RA there was no significant difference in OSCAR expression within lining, sublining and vessels (p=0.217, 0.622, 0.906 respectively) between 0 and 6 months. The expression of OSCAR in the sublining reduced in 10/15 patients by 6 months. Very few TRAP positive cells were detected at either time point. The CPJ and non-CPJ established RA cohort had higher expression of OSCAR than the early cohort. The number of TRAP positive cells was significantly higher in the CPJ versus non-CPJ (p=0.015, mean=88.5 vs 44).
Conclusions OSCAR positive cells were observed in all synovial tissues, particularly in the lining, in both early RA and established RA. This has not been previously reported. Expression of OSCAR by sublining cells including OC precursors, possibly dendritic cells, macrophages and endothelial cells is consistent with previous reports. Low numbers of TRAP positive cells may relate to early disease and/or site of biopsy as distant from the actual CPJ due to limitations of arthroscopic technique. In established RA, higher numbers of TRAP and OSCAR positive cells were present in both CPJ and non-CPJ tissues. The reduced sublining OSCAR expression in the majority of patients following treatment suggests modulation of OSCAR by DMARDS and may implicate OSCAR as an inflammation and bone erosion predictive biomarker.
Disclosure of Interest None declared