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Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [scRNA-seq]

ABSTRACT: Ossification of the posterior longitudinal ligament (OPLL) is a progressive ectopic bone formation of ligaments and may lead to severe neurological symptoms. However, in addition to conservative therapy for neurological symptoms or surgical management, effective pharmacotherapy and preventive intervention for OPLL remains absent. Here, to reveal the potential therapeutic target we generate single-cell maps of T-OPLL patients. We found that type I IFN signaling pathway is significantly activated during the progression of ossification. Further, stimulation of IFN β obviously promoted the calcium deposition of murine MC3T3-E1 preosteoblasts. We profiled the transcriptome in MC3T3-E1 cells after osteogenic induction, and found that IFN β promoted the expression of Sox9 and SPP1. STAT1 positively regulated the expression of Sox9 and phosphorylated STAT1 occupied on the promoter of Sox9. We also observed the localization of Sox9 in the ossificated region of ligament from OPLL patients. Thus, Sox9 is a target gene of type I IFN pathway during osteogenic induction. Furthermore, blockage of IFNAR1 by anti-IFNAR1 neutralizing antibody significantly impeded osteoblast differentiation induced by IFN β and display efficacy against ossification. Together, these results demonstrated that type I IFN signaling pathway promotes osteoblast differentiation. Anti-IFNAR1 neutralizing antibody could be used as a potential therapy for OPLL by blocking type I IFN signaling pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE241505 | GEO | 2023/11/30

REPOSITORIES: GEO

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Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [RNA-seq]

Project description:Ossification of the posterior longitudinal ligament (OPLL) is a progressive ectopic bone formation of ligaments and may lead to severe neurological symptoms. However, in addition to conservative therapy for neurological symptoms or surgical management, effective pharmacotherapy and preventive intervention for OPLL remains absent. Here, to reveal the potential therapeutic target we generate single-cell maps of T-OPLL patients. We found that type I IFN signaling pathway is significantly activated during the progression of ossification. Further, stimulation of IFN β obviously promoted the calcium deposition of murine MC3T3-E1 preosteoblasts. We profiled the transcriptome in MC3T3-E1 cells after osteogenic induction, and found that IFN β promoted the expression of Sox9 and SPP1. STAT1 positively regulated the expression of Sox9 and phosphorylated STAT1 occupied on the promoter of Sox9. We also observed the localization of Sox9 in the ossificated region of ligament from OPLL patients. Thus, Sox9 is a target gene of type I IFN pathway during osteogenic induction. Furthermore, blockage of IFNAR1 by anti-IFNAR1 neutralizing antibody significantly impeded osteoblast differentiation induced by IFN β and display efficacy against ossification. Together, these results demonstrated that type I IFN signaling pathway promotes osteoblast differentiation. Anti-IFNAR1 neutralizing antibody could be used as a potential therapy for OPLL by blocking type I IFN signaling pathway.

2023-11-30 | GSE241506 | GEO

Transcriptome and Micronome analysis of OPLL

Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. MicroRNAs are small nucleatides that function as regulators of gene expression in almost any biological process. However, few microRNAs are reported to have a role in the pathological process of OPLL. Therefore, we performed high-throughput microRNA sequencing and transcriptome sequencing of primary OPLL and PLL cells in order to decipher the interacting network of microRNAs in OPLL. MRNA and microRNA profiles were done using primary culture cells of human ossification of the posterior longitudinal ligament (OPLL) tissue and normal posterior longitudinal ligament (PLL) tissue.

2016-04-04 | E-GEOD-69787 | biostudies-arrayexpress

Cyclic tensile strain enhances the expression of Indian hedgehog and progression of ossification of the human cervical posterior longitudinal ligament

Project description:The initiation and/or progression of ossification of the posterior longitudinal ligament (OPLL) is associated with cyclic tensile strain, but the pathomechanism of OPLL remains unclear. Indian hedgehog (Ihh) and its related signaling are key factors in normal enchondral ossification. However, the relation of OPLL to Ihh is unclear. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relation of Ihh to OPLL. Cultured posterior longitudinal ligament cells were subjected to 24 hours of cyclic tensile strain and then analyzed by microarray.

2016-06-22 | E-GEOD-83569 | biostudies-arrayexpress

Transcriptome and Micronome analysis of OPLL

Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. MicroRNAs are small nucleatides that function as regulators of gene expression in almost any biological process. However, few microRNAs are reported to have a role in the pathological process of OPLL. Therefore, we performed high-throughput microRNA sequencing and transcriptome sequencing of primary OPLL and PLL cells in order to decipher the interacting network of microRNAs in OPLL.

2016-04-04 | GSE69787 | GEO

Identification of differentially expressed circRNAs in ossification of the posterior longitudinal ligament

Project description:Ossification of the posterior longitudinal ligament(OPLL) is a progressive abnormal calcification of the spinal ligament, which causes myelopathy and neurological symptoms. Both genetic and environmental factors play an important role in its occurrence and progress. In recent decades, many studies on OPLL have shown that it is a multifactorial disease. However, the role of circRNAs in the pathogenesis of OPLL is far from clear. In order to identify the transcriptional regulators of OPLL, we compared the expression of circRNAs in the posterior longitudinal ligament tissues from OPLL patients and healthy volunteers through microarray analysis. The analysis revealed a set of circRNAs specifically regulated in humans with heterotopic ossification of ligament tissue. These findings imply that circRNAs may play an important role in OPLL, which provides new ideas for the study of OPLL.

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Transcriptome analysis of Advanced glycation end products treated ligament cells

Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1ÂµM, 5ÂµM and negative control), with or without BMP2 (1ÂµM). mRNA profiles of Primary human posterior longitudinal ligament cells stimulated with various stimuli (Control, 1ÂµM AGE-BSA, 5ÂµM AGE-BSA, 1ÂµM AGE-BSA with BMP2, 5ÂµM AGE-BSA with BMP2) were generated by deep sequencing on Ion Proton

2016-02-16 | E-GEOD-65952 | biostudies-arrayexpress

Transcriptome analysis of Advanced glycation end products treated ligament cells

Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM).

2016-02-16 | GSE65952 | GEO

MicroRNA profiling and analysis of primary OPLL cell derived exosomes

Project description:In order to investigate the function and mechanism of Ossification of Posterior Longitudinal Ligament (OPLL) primary ligament cell derived exosomes, we take advantages of high throughput sequencing technology to fully reveal the small RNA content of both OPLL and normal posterior longitudinal ligament (PLL) cell derived exosomes.

2021-11-11 | GSE113632 | GEO

Cyclic tensile strain enhances the expression of Indian hedgehog and progression of ossification of the human cervical posterior longitudinal ligament

2016-06-22 | GSE83569 | GEO

Effect of Cyclic stretching on the gene expression in human spinal ligament cells

Project description:Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by progressive ectopic bone formation in the spinal ligament. To identify the genes related to ectopic ossification of human spinal ligament affected by mechanical stress, analyses using cDNA microarray were carried out using cultured human spinal ligament cells that had been subjected to uniaxial cyclic stretching. cDNA microarrays revealed that ranges of distribution of both up- and down-regulated genes evoked by cyclic stretching were significantly wider in cells from than in non-OPLL cells. Keywords: mechanical-stress response

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