Transcriptome profiling of osteoclast subpopulations associated with arthritis: a pathogenic role of CCR2hi osteoclast progenitors

The existence of different osteoclast progenitor (OCP) subsets has been confirmed by numerous studies. However, pathological osteoclastogenesis within the bone marrow compartment and at extramedullary sites remains incompletely understood. Detailed characterization of OCP subsets may elucidate the pathophysiology of increased osteoclast activity causing periarticular and systemic bone resorption in arthritis. We previously identified two different subpopulations of OCPs based on their expression of chemokine receptor CCR2 as CD45+Ly6G-CD3-B220-NK1.1-CD11b-/loCD115+CCR2hi (CCR2hi) and CD45+Ly6G-CD3-B220-NK1.1-CD11b-/loCD115+CCR2-/lo (CCR2lo). We FACS sorted the two subsets from non-immunized and collagen-induced arthritis mice and performed next-generation RNA sequencing. Our approach identified a disparity between CCR2hi and CCR2lo OCP subsets and differentially expressed genes that would allow detection of distinct subsets of OCPs associated with arthritis as well as indicate possible therapeutic targets aimed to modulate progenitor migration, proliferation, differentiation or activity.