Dataset Information

The influence of IL-1β and TNF-α on the tenogenic differentiation of human periodontal ligament stem cells via global proteomic analysis

ABSTRACT: The hPDLSCs were cultured in the tenogenic medium treated with 0.1 ng/ml IL-1β or 10 ng/ml TNF-α for 7 days. Total proteins were isolated from the collected cell samples. Subsequently, the LFQ-based proteomic analysis was conducted for the extracted proteins in each group as established procedures [59]. Differential expression analysis was performed by comparing the expression levels of the identified proteins in the hPDLSCs treated with IL-1β or TNF-α with those in the Ctrl group.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jialin Chen

PROVIDER: PXD056585 | iProX | Sat Oct 05 00:00:00 GMT+01:00 2024

REPOSITORIES: iProX

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Publications

Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling.

Chen Jialin J Sheng Renwang R Mo Qingyun Q Backman Ludvig J LJ Lu Zhiyuan Z Long Qiuzi Q Chen Zhixuan Z Cao Zhicheng Z Zhang Yanan Y Liu Chuanquan C Zheng Haotian H Qi Yu Y Cao Mumin M Rui Yunfeng Y Zhang Wei W

Bioactive materials 20241023

Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analys ...[more]

PMID: 39512422

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Project description:Purpose: Fibroblast-like synoviocytes (FLSs) play a crucial role in maintaining joint homeostasis by secreting matrix components and lubricin [1, 2]. However, under inflammatory conditions, FLSs contribute to tissue damage, leading to osteoarthritis (OA) [3]. The specific genes and pathways driving this inflammatory response in FLSs remain poorly understood. This study aims to elucidate the transcriptome-wide responses of FLSs to IL-1β, a master proinflammatory cytokine, and to investigate the modulatory effects of TGF-β1 on the expression of chemokine transcripts in a model of inflammatory arthritis. Methods: Normal FLSs were isolated from synovial explants obtained from patients undergoing anterior cruciate ligament reconstruction surgery. The isolated cells were expended and exposed to IL-1β (10 ng/mL) for 24 hours to simulate inflammatory arthritis. Changes in gene expression were assessed by RNA-seq and validated through Fluidigm multiplex real-time PCR [4]. In a separate experiment, FLSs were pre-treated with IL-1β as above and subsequently exposed to TGF-β1 (10 ng/mL) for an additional 48 hours to evaluate its potential modulatory effects on the expression of chemokines as determined by Fluidigm multiplex real-time PCR. Results: IL-1β-treated FLSs showed a significant upregulation of numerous chemokines, including CCL20, CCL5, CXCL8, CXCL6, CXCL4, CXCL1, CXCL3, and CXCL2. Additionally, transcripts associated with inflammatory arthritis, such as CSF2, CSF3, MMP12, IL1B, and LIPM, were elevated (Table 1). Expression of KRT14, KRT19, KRT18, and several other anabolic and matrix genes was significantly reduced with IL-1β-treatment (Table 1). The genes highly expressed in IL-1β-treated cells were enriched for NFkB signaling, cytokine and chemokine signaling, TNF signaling, and necroptosis, whereas genes lowly expressed were enriched for the immune system. TGF-β1 treatment exhibited strong anti-inflammatory effects, modulating the expression of numerous chemokines and inflammatory mediators, thereby counteracting the IL-1β-induced inflammatory response in FLSs (Fig. 1). Moreover, the expression of the chemokine transcription factor C/EBPβ was also high (about twofold) in IL-1β-treated cells, which was reduced by half after TGF-β1 treatment, suggesting that TGF-β1 exerts its anti-chemokine effects through transcriptional repression of C/EBPβ in FLSs. Conclusions: This is the first study to examine the effects of IL-1β treatment in FLS derived from patients with ACL tears. Our data show that IL-1β significantly influences the expression of CC and CXC chemokine transcripts in FLSs, mirroring findings in chondrocytes, where human adult chondrocytes exhibit increased expression of CC and CXC chemokines [5]. Our finding that TGF-β1 effectively mitigates the inflammatory responses induced by IL-1β, potentially through suppression of transcription factor C/EBPβ, is novel. It highlights the potential of TGF-β1 as a therapeutic target for OA-related inflammatory conditions. These findings warrant further mechanistic studies to understand the inflammatory dynamics of FLSs in inflammatory arthritis.

Dataset Information

The influence of IL-1β and TNF-α on the tenogenic differentiation of human periodontal ligament stem cells via global proteomic analysis

Publications

Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling.

Similar Datasets

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