The authors of this article (Hasegawa, et.al, Nat.Immun 2019) have studied the formation of osteoclasts, which play a crucial role in arthritic bone erosion. They have developed an original protocol to isolate the inflamed synovium from arthritic mice and have identified specific macrophages called arthritis-associated osteoclastogenic macrophages (AtoMs) as osteoclast precursors in arthritic joints. AtoMs are a subset distinct from the osteoclast precursors in bone marrow. Transcription profiling using RNA sequencing experiments enabled them to establish that the transcription factor FoxM1 is a key regulator responsible for the differentiation of AtoM macrophages into osteoclasts in the synovium. Single-cell mRNA sequencing experiments performed using the BD Rhapsody™ system and t-distributed stochastic neighbourhood embedding (t-SNE) enabled the clustering of cells based on gene expression. From this, it was possible to identify clusters in which osteoclast-related genes were highly expressed. From these and other experiments, the authors could establish that rheumatoid arthritis synovial AtoM macrophages had high osteoclastogenic potential and FoxM1 constitutes a potential target for treatment.
Read the article online here.