Zinc finger protein A20 regulates the development and progression of osteoarthritis by affecting the activity of NF-κB p65

Cui, Shubei; Wang, Tao-Xia; Liu, Zhen-Wu; Yan, Ji-Ying; Zhang, Kai

doi:10.1080/08923973.2021.1970764

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…Conversely, ZNF521 exerts its anti-OA effects by regulating the levels of nuclear histone deacetylase 4 [ 27 ]. Additionally, ZNFA20 exhibits reduced expression in OA cartilage samples [ 28 ]. However, its overexpression has been shown to ameliorate extracellular matrix degradation and apoptosis in chondrocytes in vitro, as well as reduce inflammation in OA mice.…”

Section: Discussionmentioning

confidence: 99%

Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization

Li,

Guan,

et al. 2024

Clin Rheumatol

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Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders and a primary cause of pain and disability among the elderly population. Research on the relationship between metalloproteins (MPs) and OA is limited, and causality remains unclear. Our objective is to utilize Mendelian randomization (MR) to explore the possible causal relationship between MPs and OA. The data on MPs were derived from a Genome-Wide Association Study (GWAS) analysis involving 3301 samples. The GWAS data for OA were obtained from an analysis involving 462,933 European individuals. In this study, a variety of two-sample Mendelian randomization methods (two-sample MR) to evaluate the causal effect of MPs on OA, including inverse variance weighted method (IVW), MR-Egger method, weighted median method (WM), simple mode, weight mode, and Wald ratio. The primary MR analysis using the IVW method reveals a significant negative correlation between Metallothionein-1F (MT-1F), zinc finger protein 134 (ZNF134), calcium/calmodulin-dependent protein kinase type 1D (CAMK1D), and EF-hand calcium-binding domain-containing protein 14 (EFCAB14) with the occurrence of osteoarthritis (OA) (p value < 0.05). However, no causal relationship was observed in the opposite direction between these MPs and OA. Notably, even in combined models accounting for confounding factors, the negative association between these four MPs and OA remained significant. Sensitivity analysis demonstrated no evidence of horizontal pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the results. In this study, we have established a conspicuous association between four distinct MPs and OA. This discovery augments our understanding of potential avenues for the diagnosis and treatment of this condition. Key Points• The MR method was employed to assess the relationship between MPs and OA.• A total of four types of MPs have demonstrated inhibitory effects on the occurrence of OA.

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Section: Discussionmentioning

confidence: 99%

Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization

Li,

Guan,

et al. 2024

Clin Rheumatol

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“…Additionally, genes encoding for zinc finger proteins (ZNFs), such as ZNF669, ZNF510, and ZNF16, were differentially expressed. ZNFs have been demonstrated to modulate the NF-κB signalling pathway by either repressing or activating transcription factor activity [43,46], but they are also capable of binding metals [47]. Potentially, the here-observed upregulation of genes encoding zinc and iron-chelating proteins is a consequence of increased intracellular zinc and iron to toxic levels, which were generated by the chelating actions of PDTC.…”

Section: Discussionmentioning

confidence: 99%

Serum Induces the Subunit-Specific Activation of NF-κB in Proliferating Human Cardiac Stem Cells

Schmidt,

Höving,

Nowak

et al. 2024

IJMS

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Cardiovascular diseases (CVDs) are often linked to ageing and are the major cause of death worldwide. The declined proliferation of adult stem cells in the heart often impedes its regenerative potential. Thus, an investigation of the proliferative potential of adult human cardiac stem cells (hCSCs) might be of great interest for improving cell-based treatments of cardiovascular diseases. The application of human blood serum was already shown to enhance hCSC proliferation and reduce senescence. Here, the underlying signalling pathways of serum-mediated hCSC proliferation were studied. We are the first to demonstrate the involvement of the transcription factor NF-κB in the serum-mediated proliferative response of hCSCs by utilizing the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). RNA-Sequencing (RNA-Seq) revealed ATF6B, COX5B, and TNFRSF14 as potential targets of NF-κB that are involved in serum-induced hCSC proliferation.

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“…Inflammatory factors play an important role in promoting the progression of OA, especially IL-1β and IL-6 play a key role in the pathological process of OA [ 31 , 32 ]. IL-1β and IL-6 could stimulate the production of pain factors such as NO, iNOS and prostaglandin E2 (PGE2) [ 31 , 33 , 34 ]. These pain factors were highly expressed in OA and were significantly related to the progression of OA.…”

Section: Discussionmentioning

confidence: 99%

miR-181a-5p targets DDX3X to inhibit the progression of osteoarthritis via NF-ΚB signaling pathway

Zhao

2023

J Orthop Surg Res

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Osteoarthritis (OA) is the most common age-related joint disease, characterized by chronic inflammation, progressive articular cartilage destruction and subchondral osteosclerosis. More and more evidence showed that microRNAs (miRNAs) play a key role in various diseases, but the specific mechanism of miRNAs in OA is not clear. The purpose of this study was to investigate the expression level and role of miR-181a-5p in OA and its related mechanism. Here we identified the key gene DEAD-box RNA helicase 3X (DDX3X) in the OA dataset by bioinformatics analysis. At the same time, miRNAs targeting DDX3X were screened, and miR-181a-5p was selected as the next research object. Then we used different concentrations of interleukin-1 beta (IL-1β)-induced in vitro model of arthritis, and found that IL-1β can stimulate cells to release nitric oxide. The expression levels of miR-181a-5p and DDX3X in mouse chondrocyte cell line ATDC5 induced by IL-1β at a concentration of 10ug/mL were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). IL-1β induced a decrease in the expression of miR-181a-5p and an increase in the expression of DDX3X in ATDC5 cells. mimic miR-181a-5p or inhibitor miR-181a-5p were transfected into ATDC5 cells, and the levels of inflammatory mediators in the cells were detected by enzyme-linked immunosorbent assay, and the results showed that miR-181a-5p could reduce the release of tumor necrosis factor-α, IL-1β, IL-6 and inducible nitric oxide nitric oxide synthase in a cellular model of arthritis. Luciferase reporter assays confirmed that the miR-181a-5p binding site was in the DDX3X gene 3′-untranslated region (3′-UTR), and DDX3X was negatively regulated by miR-181a-5p. Rescue assays confirmed that miR-181a-5p reduced the expression of DDX3X by targeting the 3′-UTR region of DDX3X, thereby reducing the release of inflammatory factors. Finally, in this paper, western blot was used to detect the mechanism of miR-181a-5p regulating OA. The results showed that interfering with the expression of miR-181a-5p could up-regulate the expression of DDX3X protein, increase the expression of nuclear factor- kappaB (NF-κB) related proteins, and reduce the inflammatory response of OA, thereby increasing the secretion of the matrix proteinases MMP-3 and MMP-13. Taken together, the results of the study suggested that miR-181a-5p may be a promising therapeutic target for the treatment of human OA.

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Zinc finger protein A20 regulates the development and progression of osteoarthritis by affecting the activity of NF-κB p65

Cited by 9 publications

References 47 publications

Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization

Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization

Serum Induces the Subunit-Specific Activation of NF-κB in Proliferating Human Cardiac Stem Cells

miR-181a-5p targets DDX3X to inhibit the progression of osteoarthritis via NF-ΚB signaling pathway

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