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

作　　者：Xiao Liu Lei Zhang Ge Wang Wei Zhao Chen Liang Youzhi Tang Yenan Fu Bo Liu Jing Zhang Xiaoguang Liu Hongquan Zhang Yu Yu 

机构地区：[1]Department of Orthopedics and Beijing Key Laboratory of Spinal Disease Research,Peking University Third Hospital,Beijing,100191,China [2]Department of Human Anatomy,Histology and Embryology,School of Basic Medical Sciences,State Key Laboratory of Molecular Oncology and International Cancer Institute,Peking University Health Science Center,Beijing,100191,China

出　　处：《Frontiers of Medicine》2024年第6期1087-1099,共13页医学前沿(英文版)

基　　金：supported by grants from the Ministry of Science and Technology of the People’s Republic of China(No.2022YFA1104003 to Hongquan Zhang and No.2021YFC2501003 to Hongquan Zhang);the National Natural Science Foundation of China(No.82073076 to Yu Yu,No.82372992 to Yu Yu,No.82230094 to Hongquan Zhang and No.81972616 to Hongquan Zhang,and No.82372451 to Xiaoguang Liu).

摘　　要：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-βstimulation 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/βsubunit 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.

关 键 词：OSSIFICATION posterior longitudinal ligament osteogenic differentiation IFN signaling 

分 类 号：R394[医药卫生—医学遗传学]