Integrative single cell RNA-sequencing and spatial transcriptomics uncovers distinct macrophage-fibroblast cross-talk in human hip synovium between patients with femoroacetabular impingement and osteoarthritis

Importantly, analysis of cell-cell interactions indicates that fibroblast growth factor 2 (FGF2) secreted from COL1A1+IGFBP5+ fibrotic macrophages may signal through syndecan 4 (SDC4) expressed by EREG+ lining FLS, inducing the expression of IL6, IL8, MMP1, and PTGS2. The GO term analysis of activated genes downstream of FGF2-SDC4 signaling revealed that biological processes associated with inflammation and angiogenesis were upregulated in hip OA, while mechanical stimulus and skeletal muscle differentiation were dominant in FAI.

Moreover, we also found that EREG+CCL20+MMP3hi lining FLS as well as most macrophage and monocyte populations are unique to hip OA patients when compared to knee OA and RA patients. The findings of this study offer a groundwork in tailoring novel targets and therapies for FAI and hip OA patients.