Identification of a potential gene target for osteoarthritis based on bioinformatics analyses

Duan, Zhixi; Li, Yusheng; Tu, Chao; Xie, Peng; Li, Yi-Han; Qi, Lin; Li, Zhihong

doi:10.1186/s13018-020-01756-w

Cited by 6 publications

(4 citation statements)

References 38 publications

(42 reference statements)

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“…Hu Y et al [ 32 ] screened three hub genes (CX3CR1, MYC, and TLR7) and identified potential drugs for the treatment of OA. Duan ZX et al [ 33 ] not only identified PTHLH as the most relevant gene for OA but also further tested and determined PTHLH levels in the plasma and synovial fluid of knee joints of OA patients. In our study, based on the FerrDb database and GEO dataset, the hub gene SLC3A2 was screened, and its function was verified by a series of cellular experiments.…”

Section: Discussionmentioning

confidence: 99%

Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments

Liu

Deng

et al. 2022

Cells

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Osteoarthritis (OA) is a type of arthritis that causes joint pain and limited mobility. In recent years, some studies have shown that the pathological process of OA chondrocytes is related to ferroptosis. Our study aims to identify and validate differentially expressed ferroptosis-related genes (DEFRGs) in OA chondrocytes and to investigate the potential molecular mechanisms. RNA-sequencing and microarray datasets were downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed genes (DEGs) were screened by four methods: limma-voom, edgeR, DESeq2, and Wilcoxon rank-sum test. Weighted correlation network analysis (WGCNA), protein-protein interactions (PPI), and cytoHubba of Cytoscape were applied to identify hub genes. Clinical OA cartilage specimens were collected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, western blotting (WB), histological staining, transmission electron microscopy (TEM), and transfection. Sankey diagram was used to visualize the relationships between the expression level of SLC3A2 in the damaged area and clinical factors. Based on bioinformatics analysis, clinical factors, and experiment validation, SLC3A2 was identified as a hub gene. It was down-regulated in OA cartilage compared to normal cartilage (p < 0.05). Functional enrichment analysis revealed that SLC3A2 was associated with ferroptosis-related functions. Spearman correlation analysis showed that the expression level of SLC3A2 in the OA cartilage-damaged area was closely related to BMI, obesity grade, and Kellgren-Lawrence grade. Furthermore, in vitro experiments validated that SLC3A2 inhibited ferroptosis and suppressed cartilage degeneration in OA. In summary, we demonstrated that SLC3A2 inhibited ferroptosis and suppressed cartilage degeneration in OA. These findings provide a new idea for the study of the pathogenesis of OA, thus providing new means for the clinical diagnosis and targeted therapy of OA.

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Section: Discussionmentioning

confidence: 99%

Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments

Liu

Deng

et al. 2022

Cells

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“…Specifically, we downloaded the data with accession numbers GSE12021, GSE55235, 26 and GSE55457. 27 The samples included in our study were sourced from Homo sapiens.…”

Section: Methodsmentioning

confidence: 99%

Risk factor prediction and immune correlation analysis of cuproptosis‐related gene in osteoarthritis

Che,

Yang,

Zhao

et al. 2024

J Cellular Molecular Medi

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Osteoarthritis (OA) is a widespread inflammatory joint disease with significant global disability burden. Cuproptosis, a newly identified mode of cell death, has emerged as a crucial factor in various pathological conditions, including OA. In this context, our study aims to investigate the intrinsic relationship between cuproptosis‐related genes (CRGs) and OA, and assess their potential as biomarkers for OA diagnosis and treatment. Datasets from the GEO databases were analysed the differential expression of CRGs, leading to the identification of 10 key CRGs (CDKN2A, DLD, FDX1, GLS, LIAS, LIPT1, MTF1, PDHA1, DLAT and PDHB). A logistic regression analysis and calibration curves were used to show excellent diagnostic accuracy. Consensus clustering revealed two CRG patterns, with Cluster 1 indicating a closer association with OA progression. RT‐PCR confirmed a significant increase in the expression levels of these nine key genes in IL‐1β‐induced C28/i2 cells, and the expression of CDKN2A and FDX1 were also elevated in conditioned monocytes, while the expression of GLS and MTF1 were significantly decreased. In vitro experiments demonstrated that the expression levels of these 7/10 CRGs were significantly increased in chondrocytes induced by IL‐1β, and upon stimulation with cuproptosis inducers, chondrocyte apoptosis was exacerbated, accompanied by an increase in the expression of cuproptosis‐related proteins. These further substantiated our research findings and indicated that the nine selected cuproptosis genes have high potential for application in the diagnosis of OA.

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“…Mice primary chondrocytes were isolated and cultured as previously reported (Duan et al, 2020). In brief, cartilage tissues from the mice were cut into small pieces under sterile conditions.…”

Section: Isolation and Culture Of Chondrocytes From Tibial And Verteb...mentioning

confidence: 99%

Leptin differentially regulate cell apoptosis and cycle by histone acetylation in tibial and vertebral epiphyseal plates

et al. 2022

Cell Biology International

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Leptin showed different apoptosis regulation effects on the chondrocytes from tibial and vertebral epiphyseal plates. However, the mechanism is still unclear. In this study, we tested the protein profile of tibial and vertebral epiphyseal plate chondrocytes with and without leptin stimulation by mass spectrometry and found that the histone acetylation level of tibial chondrocytes was decreased after leptin treatment, while increased in vertebral epiphyseal plates. COIP assay showed that leptin promoted H3, H4 histone acetylation by recruiting CREB binding protein (CBP)/P300 to activate histone acetyl transferases (HATs) activity in vertebral disc chondrocytes. But in tibial plate cartilage cells, leptin did not recruit CBP and p300, thus differently affect the apoptosis of epiphyseal plate chondrocytes. Through explored the mechanism of histone acetylation modulated by leptin, and its effect on cartilage cell apoptosis and cell cycle regulation, This provides a novel target therapy possibility therapeutic approach to for the related disease.

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Identification of a potential gene target for osteoarthritis based on bioinformatics analyses

Cited by 6 publications

References 38 publications

Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments

Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments

Risk factor prediction and immune correlation analysis of cuproptosis‐related gene in osteoarthritis

Leptin differentially regulate cell apoptosis and cycle by histone acetylation in tibial and vertebral epiphyseal plates

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