Single-cell transcriptome profiling identifies the activation of type I interferon signaling in ossified posterior longitudinal ligament

Front Med. 2024 Dec;18(6):1087-1099. doi: 10.1007/s11684-024-1075-5. Epub 2024 Oct 23.

Abstract

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.

Keywords: IFN signaling; ossification; osteogenic differentiation; posterior longitudinal ligament.

MeSH terms

  • Cell Differentiation
  • Female
  • Gene Expression Profiling*
  • Humans
  • Interferon Type I* / metabolism
  • Male
  • Middle Aged
  • Ossification of Posterior Longitudinal Ligament* / genetics
  • Osteogenesis* / genetics
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction*
  • Single-Cell Analysis*

Substances

  • Interferon Type I
  • Receptor, Interferon alpha-beta