GSE123492
RNA-sequencing of highly pure synovial tissue macrophages reveals two distinct osteoarthritis subgroups that indicate different disease mechanisms.
Osteoarthritis (OA) is a leading cause of disability globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target inflammation therapeutically have had limited success. A better understanding of the cellular and molecular processes occurring in the OA synovium is needed to develop novel therapeutic strategies. Here, we contrasted mononuclear phagocytes and T cells in the synovial tissue of OA patients and inflammatory-arthritis (IA) patients. Compared to IA, OA synovial tissue contained fewer CD45+ leukocytes, consisting mostly of macrophages. Macrophages in OA synovial tissues displayed activated phenotypes shown by expression of proteins folate-receptor-2 and CD86. Macrophage phenotype, proliferation characteristics and transcriptome profile by RNA-sequencing distinguished two subtypes of patients within OA. One subgroup was more similar to IA - 'inflammatory-like OA' (iOA), and another non-inflammatory/mechanical, subgroup distinct from IA - 'classical OA' (cOA). Gene Ontology (GO) pathway analysis revealed that the iOA subgroup is characterised by a cell proliferation signature, whereas the cOA subgroup is defined by cartilage remodelling features. Furthermore, iOA synovial tissue contained higher proportions of macrophages, expressing higher levels of the proliferation marker Ki-67, as compared to cOA synovial tissue. The identification of these two distinct OA subtypes provides new insight into the heterogeneity of OA at the synovial tissue level, and suggests distinct cellular mechanisms in disease pathogenesis. Our findings could lead to the stratification of OA patients for suitable disease-modifying treatments, and the identification of novel therapeutic targets. Overall design: RNA sequencing of 12 FACS purified macrophage samples isolated from synovial tisssue of arthritis patients