Deciphering the Osteoimmune Landscape in Subtalar Arthrodesis: A Single-Cell RNA Sequencing Approach

Abstract

Subtalar arthrodesis (SA) is a widely used salvage procedure for posttraumatic subtalar arthritis (PSA), but its underlying healing mechanisms remain poorly understood. The immune system plays a critical role in the union process after arthrodesis; however, the systemic osteoimmunological response has not been clearly defined. In this study, we investigated immune cell dynamics in patients who underwent SA using single-cell RNA sequencing (scRNA-seq). Peripheral blood mononuclear cells (PBMCs) were collected before surgery and 3 months after the operation. The degree of bone fusion was assessed using computed tomography (CT) scans at 3 months, and patients were categorised into early union (EU) and delayed union (DU) groups. scRNA-seq analysis was performed to examine immune cell composition, gene expression and functional pathways. Monocytes in the EU group showed enhanced antigen processing and presentation, whereas those in the DU group demonstrated increased phagocytic activity. NK cells in the DU group exhibited stronger cytotoxicity through Fc-gamma receptor signalling and antibody-dependent cellular cytotoxicity (ADCC) pathways, while NK cells in the EU group showed higher chemokine and cytokine activity. These immune differences persisted postoperatively, suggesting that variations in the systemic immune environment may influence bone healing outcomes. Our findings emphasise the important roles of monocytes and NK cells in bone union and suggest that immunomodulatory approaches could help improve bone repair.