Single-cell transcriptome profiling identifies the activation of type I interferon signaling in ossified posterior longitudinal ligament.
10.1007/s11684-024-1075-5
- Author:
Xiao LIU
1
;
Lei ZHANG
2
;
Ge WANG
2
;
Wei ZHAO
2
;
Chen LIANG
1
;
Youzhi TANG
2
;
Yenan FU
2
;
Bo LIU
2
;
Jing ZHANG
2
;
Xiaoguang LIU
3
;
Hongquan ZHANG
4
;
Yu YU
5
Author Information
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.
3. Department of Orthopedics and Beijing Key Laboratory of Spinal Disease Research, Peking University Third Hospital, Beijing, 100191, China. xglius@vip.sina.com.
4. 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. hongquan.zhang@bjmu.edu.cn.
5. 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. yuyu@bjmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
IFN signaling;
ossification;
osteogenic differentiation;
posterior longitudinal ligament
- MeSH:
Humans;
Signal Transduction;
Interferon Type I/metabolism*;
Ossification of Posterior Longitudinal Ligament/genetics*;
Gene Expression Profiling;
Single-Cell Analysis;
Osteogenesis/genetics*;
Receptor, Interferon alpha-beta/metabolism*;
Male;
Female;
Cell Differentiation;
Middle Aged
- From:
Frontiers of Medicine
2024;18(6):1087-1099
- CountryChina
- Language:English
-
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.
