Activation of the interferon pathway identified as the major driver of OPLL pathogenesis

Ossification of the posterior longitudinal ligament (OPLL) is a progressive spinal disease characterized by ectopic bone formation of the spine, resulting in severe neurological symptoms due to spinal compression. This condition is more common in Asian countries and is associated with a variety of genetic and hormonal factors.

Recent insights reveal a potential role for interferon (IFN) signaling in the pathogenesis of OPLL, particularly in the type I IFN pathway known to play a role in the innate immune response and bone formation. I’m doing it. Single-cell transcriptome profiling studies have identified activation of type I IFN signaling in the post-bone longitudinal ligaments, suggesting a therapeutic target for OPLL.

This study included recruiting patients with T-OPLL and contrasting patients from Peking University Hospital 3, with existing ligament tissue obtained from surgical procedures. Single-cell RNA sequencing (SCRNA-Seq) was performed to analyze cell population characteristics and pathological gene expression patterns. This analysis revealed a clear subpopulation with transcription signatures, indicating one cluster showing enrichment of type I IFN-related responses in OPLL patients.

It is known that the type I IFN signaling pathway is activated during the progression of ossification, such as OAS2, OAS3, IRF7, MX1, MX2, and STAT1, showing higher expression levels in ossified tissues. Ta. Further in vitro experiments using mouse MC3T3-E1 preosteoblasts showed that IFN-β promotes osteogenic differentiation and calcium deposition, suggesting a role for the type I IFN pathway in osteogenesis. Blocking the type I IFN pathway using anti-IFNAR1 neutralizing antibodies has been found to be effective in inhibiting ossification, indicating a potential therapeutic strategy for OPLL.

The results of this study provide a comprehensive understanding of cellular and molecular changes in OPLL and highlight the importance of the type I IFN pathway in the pathogenesis of disease. Its role in promoting activation of this pathway and osteogenic differentiation in ossified tissues provides a new perspective on the treatment of OPLL. By targeting the type I IFN pathway, it may be possible to develop new therapeutic interventions that may arrest or reverse the progression of this debilitating disease. The results of this study contribute to increased knowledge about the role of IFN signaling in bone disease, paving the way for future research into the development of targeted therapies for OPLL.