Single-cell RNA-sequencing analysis reveals cellular states and intercellular communication of human lumbar facet-joint degeneration

BACKGROUNDFacet joint osteoarthritis (FJOA) is a chronic degenerative joint disease, which can lead to severe low back pain.However, the pathophysiological mechanisms underlying the degenerative progression in human lumbar FJOA remain undefined. AIMTo investigate the cellular heterogeneity, potential therapeutic markers, and underlying mechanisms of human lumbar facet joint (LFJ) degeneration. METHODSWe determined the cell landscapes of human LFJ cartilage using single-cell RNA sequencing. RESULTSThe proportions of proliferative chondrocytes and proinflammatory chondrocytes were significantly increased in mild degenerated LFJ samples, while those of fibrocartilage chondrocytes, effector chondrocytes, and homeostatic chondrocytes were increased in severe degenerated LFJs.Importantly, proinflammatory chondrocytes were found in mild degenerated LFJs, but not in severe degenerated LFJs.We also found that severe degenerated LFJs exhibited a significant increase in macrophages of five distinct subclusters: (1) Mφ-F13A1; (2) Mφ-TCN2; (3) Mφ-COL27A1; (4) Mφ-CD52; and (5) Mφ-IL3RA.Mφ-IL3RA was only identified in severe degenerated LFJs, implying its importance in the degenerative process.Cell crosstalk analysis revealed signaling pathways and changes in intercellular interactions during LFJ degeneration.Intercellular interactions between chondrocytes and macrophages were significantly greater in severe degenerated LFJs.Further analysis of the ligand-receptor interactions revealed that the increased crosstalk between chondrocytes and macrophages in severe degenerated LFJs was 5 / 39 mainly associated with inflammation-remodeling-related and tissue-remodelingrelated signaling pathways.These findings also showed progressively increased communication strength with degeneration, suggesting that chondrocytemacrophage crosstalk becomes increasingly active during LFJ cartilage degeneration. CONCLUSIONOur findings deepen the understanding and extend distinguishing features of cellular heterogeneity and intercellular interactions of LFJ cartilage, potentially contributing to new therapeutic strategies for human FJOA.