Ossification of the posterior longitudinal ligament (OPLL) is a progressive spinal disease characterized by ectopic bone formation in the spine, leading to severe neurological symptoms due to spinal cord compression. This condition is more prevalent in Asian countries and has been associated with various genetic and hormonal factors. Recent insights reveal the potential role of interferon (IFN) signaling in the pathogenesis of OPLL, particularly the type I IFN pathway, which is known to play a role in innate immune responses and bone formation. A single-cell transcriptome profiling study has identified the activation of type I IFN signaling in ossified posterior longitudinal ligament, suggesting a therapeutic target for OPLL.

The study involved the recruitment of patients with T-OPLL and control patients from Peking University Third Hospital, with ossified ligament tissues obtained from surgical procedures. Single-cell RNA sequencing (scRNA-seq) was performed to analyze cell population characteristics and pathological gene expression patterns. The analysis revealed distinct subpopulations with transcriptional signatures, with one cluster showing enrichment of type I IFN-related responses in patients with OPLL. The type I IFN signaling pathway was found to be activated during the progression of ossification, with IFN-related genes such as OAS2, OAS3, IRF7, MX1, MX2, and STAT1 exhibiting higher expression levels in ossified tissues. Further in vitro experiments using murine MC3T3-E1 preosteoblasts demonstrated that IFN-β promotes osteogenic differentiation and calcium deposition, suggesting a role for the type I IFN pathway in bone formation. Blockade of the type I IFN pathway using an anti-IFNAR1 neutralizing antibody was found to be effective in suppressing ossification, indicating a potential therapeutic strategy for OPLL.

The findings of this study provide a comprehensive understanding of the cellular and molecular changes in OPLL and highlight the significance of the type I IFN pathway in the disease's pathogenesis. The activation of this pathway in ossified tissues and its role in promoting osteogenic differentiation offer a new perspective on the treatment of OPLL. By targeting the type I IFN pathway, it may be possible to develop novel therapeutic interventions that could halt or reverse the progression of this debilitating disease. This study's results contribute to the growing body of knowledge on the role of IFN signaling in bone diseases and pave the way for future research into the development of targeted therapies for OPLL.
DOI: 10.1007/s11684-024-1075-5