| 1. |
- Chang, Yanhai, et al.
(författare)
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Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling
- 2017
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Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 91, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Mycotoxin T-2 exerts a causative role in Kashin-Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1ß in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1ß in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1ß were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1ß antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1β further aggravated cell damage in response to T-2. Additionally, cessation of IL-1β rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1β stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/β-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1β inhibition, but further enhanced following IL-1β precondition. Importantly, blocking this pathway by transfection with β-catenin alleviated the adverse roles of IL-1β on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy.
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| 2. |
- Ning, Yujie, et al.
(författare)
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Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China
- 2022
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.Methods: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.Results: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.Conclusion: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.
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| 3. |
- Ning, Yujie, et al.
(författare)
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Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy
- 2022
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.
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| 4. |
- Wang, Xiaoqing, et al.
(författare)
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Inhibiting the aberrant activation of Wnt/β-catenin signaling by selenium supplementation ameliorates deoxynivalenol-induced toxicity and catabolism in chondrocytes
- 2020
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Ingår i: Journal of Cellular Physiology. - : Wiley-Blackwell. - 0021-9541 .- 1097-4652. ; 235:5, s. 4434-4442
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Tidskriftsartikel (refereegranskat)abstract
- Kashin-Beck disease (KBD) is an endemic degenerative osteoarticular disorder associated with physical disability and a heavy economic burden. Contamination by mycotoxin deoxynivalenol (DON) and selenium deficiency have been proposed to be key etiological factors for KBD, and can work together to aggravate the progression of KBD. Nevertheless, the mechanism of DON in KBD remains elusive. In the present study, exposure to DON dose-dependently suppressed cell viability and expression of pro-proliferation marker PCNA in human chondrocytes, whereas it enhanced lactate dehydrogenase release, cell apoptosis, and caspase-3/9 activity. In addition, DON incubation shifted metabolism homeostasis towards catabolism by suppressing the transcription of collagen II and aggrecan, and the production of sulphated glycosaminoglycans and TIMP-1, while increasing matrix metalloproteinase levels (MMP-1 and MMP-13). Mechanistically, DON exposure induced the activation of Wnt/β-catenin signaling. Intriguingly, blocking this pathway reversed the adverse effects of DON on cytotoxic damage and metabolism disruption to catabolism. Notably, supplementation with selenium reduced DON-induced activation of the Wnt/β-catenin pathway. Moreover, selenium addition abrogated cytotoxic injury and excessive pro-catabolic gene expression in chondrocytes upon DON conditions. These findings confirm that DON may facilitate the development of KBD by inducing cell injury, inhibiting matrix synthesis, and increasing cellular catabolism by activating the Wnt/β-catenin signaling, which were partially reversed by selenium supplementation. Thus, the current study may presents a new viewpoint for how selenium supplementation ameliorates the development of KBD by inhibiting DON-induced cytotoxic injury and metabolism imbalance in chondrocytes.
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