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Lef1 Ablation Alleviates Cartilage Mineralization during Post-traumatic Osteoarthritis

ABSTRACT: Lef1 Ablation Alleviates Cartilage Mineralization during Post-traumatic Osteoarthritis

PROVIDER: PRJNA824872 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18689864.fastq.gz	Fastqsanger.gz
	SRR18689865.fastq.gz	Fastqsanger.gz
	SRR18689866.fastq.gz	Fastqsanger.gz
	SRR18689867.fastq.gz	Fastqsanger.gz
	SRR18689868.fastq.gz	Fastqsanger.gz

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Lef1 Ablation Alleviates Cartilage Mineralization during Post-traumatic Osteoarthritis

2022-05-16 | GSE200522 | GEO

Lef1 ablation alleviates cartilage mineralization following posttraumatic osteoarthritis induction.

Project description:Cartilage mineralization is a tightly controlled process, imperative for skeletal growth and fracture repair. However, in osteoarthritis (OA), cartilage mineralization may impact the joint range of motion, inflict pain, and increase chances for joint effusion. Here we attempt to understand the link between inflammation and cartilage mineralization by targeting Sirtuin 1 (SIRT1) and lymphoid enhancer binding factor 1 (LEF1), both reported to have contrasting effects on cartilage. We find that inflammatory-dependent cleavage of SIRT1 or its cartilage-specific genetic ablation, directly enhanced LEF1 expression accompanied by a catabolic response. Applying a posttraumatic OA (PTOA) model to cartilage-specific Sirt1 nulls displayed severe OA, which was accompanied by synovitis, meniscal mineralization, and osteophyte formation of the lateral joint compartment. Alternatively, cartilage-specific Lef1 nulls presented reduced lateral mineralization, OA severity, and local pain. Differential gene expression analysis revealed that Lef1 ablation reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Toll-like receptor (Tlr) pathways, while enhancing SRY-Box transcription factor 9 (Sox9) and cartilaginous extracellular matrix genes. The results support a link between inflammation and Lef1-dependent cartilage mineralization, mediated by the inactivation of Sirt1. By ablating Lef1 in a PTOA model, the structural and pain-related phenotypes of OA were reduced, in part, by preventing cartilage mineralization of the lateral joint compartment, partially manifested by meniscal tissue mineralization. Overall, these data provide a molecular axis to link between inflammation and cartilage in a PTOA model.

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Transcriptional profiling of articular cartilage in a porcine model of early post-traumatic osteoarthritis

Project description:36 Yucatan minipigs underwent anterior cruciate ligament (ACL) transection and were randomly assigned in equal numbers to no further treatment, reconstruction or ligament repair. Cartilage was harvested at 1 and 4 weeks post-operatively and histology and RNA-sequencing performed. The generated data served to identify the molecular pathophysiology present in early post-traumatic osteoarthritis (PTOA), as well as differences between surgical treatments.

2017-10-22 | E-MTAB-5879 | biostudies-arrayexpress

Bulk RNA-seq analyses of mandibular condylar cartilage in a post-traumatic temporomandibular joint osteoarthritis rabbit model

Project description:We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells from post-traumatic temporomandibular joint osteoarthritis model to investigate the signaling pathways critical for cellular functions during temporomandibular joint osteoarthritis pathology.

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LEF1 in Burkitt lymphoma

Project description:Recently global gene expression profiling of patients samples lead to a molecular definition of Burkitt Lymphoma (BL) with lymphocyte enhancer-binding factor 1 (LEF1) as a signature gene. Here we report the discovery of nucleic LEF1 in a very high proportion of BL cases (15/18) and LEF1 target genes. Germinal center B cells were devoid of detectable nuclear LEF1 expression as mantle cell lymphoma (0/5), marginal zone lymphoma (0/6), follicular lymphoma (0/12) or diffuse large B cell lymphoma (DLBCL) (1/31). Using whole genome gene expression profiling after transient knockdown of LEF1 in BL cell lines, new LEF1 target genes were identified. The joint expression of these genes in primary BL samples shows that LEF1 is not only expressed aberrantly in BL but also transcriptionally active. Our study identified aberrantly expressed LEF1 and its target genes suggesting an important functional role in BLs. 3 biological replicates scrb siRNA vs LEF1 si RNA , 4 siRNA are pooled

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Investigating the role of Lef1 in mouse embryonic stem cells.

Project description:Genome-wide analysis of gene expression in piggybac empty vector and piggybac-lef1 transfected mouse embryonic stem cells (46C mouse ESCs) Analysis of genes regulated by lef1, and we found that lef1 acts biphasically in mouse embryonic stem cells. Total RNA obtained from empty vector (PB)-transfected 46 ESCs or different states (passage 2 and passage 5) of lef1-transfected (PB-Lef1 P2, PB-Lef1 P5) 46C mouse ESCs.

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Transcriptional Profiling of Synovium in a Porcine Model of Early Post-traumatic Osteoarthritis

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