SPP1 secreted by nucleus pulposus cells mediates inflammatory infiltration and contributes to intervertebral disc degeneration

Low back pain resulting from intervertebral disc degeneration has emerged as a global public health challenge, imposing a substantial economic and societal burden. The inflammatory response of nucleus pulposus cells and the imbalance of the extracellular matrix are recognized as key drivers of intervertebral disc degeneration. In this study, we identified that SPP1 is highly expressed in degenerated nucleus pulposus tissue and is closely associated with both inflammation and extracellular matrix imbalance. Single-cell RNA sequencing of nucleus pulposus tissue revealed a distinct subtype of nucleus pulposus cells with high SPP1 expression, further confirming the strong association between SPP1+ nucleus pulposus cells and nucleus pulposus inflammation. Furthermore, our study demonstrates that SPP1 mediates the inflammatory response in nucleus pulposus cells through the PI3K/AKT/NF-κB signaling pathway. Additionally, SPP1 was found to enhance the secretion of inflammatory cytokines by macrophages, potentially exacerbating inflammatory infiltration in the nucleus pulposus. In summary, our findings highlight the crucial role of SPP1 in nucleus pulposus inflammation and suggest that it may serve as a promising target for the early diagnosis and treatment of intervertebral disc degeneration.