Inhibiting the aberrant activation of Wnt/β‐catenin signaling by selenium supplementation ameliorates deoxynivalenol‐induced toxicity and catabolism in chondrocytes

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 proproliferation 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 DONinduced cytotoxic injury and metabolism imbalance in chondrocytes. K E Y W O R D S chondrocyte cytotoxic damage, deoxynivalenol, Kashin-Beck disease, metabolism disorder, selenium

miR‐29a‐3p promotes migration and invasion in ameloblastoma via Wnt/β‐catenin signaling by targeting catenin beta interacting protein 1

“…Both MMP1 and MMP14 are transmembrane MMPs that are critically involved in extracellular matrix proteolysis, cellular migration, and invasion. 36,37 They are two of the downstream molecules of Wnt/β-catenin signaling. 36,37 High expressions of tumor-derived MMP1 and MMP14 have been found to contribute to malignant and invasive tumor growth.…”

“…36,37 They are two of the downstream molecules of Wnt/β-catenin signaling. 36,37 High expressions of tumor-derived MMP1 and MMP14 have been found to contribute to malignant and invasive tumor growth. [38][39][40][41][42] In addition, MMP1 and MMP14 were overexpressed in AB and associated with AB tumor behavior.…”

Deoxynivalenol: Emerging Toxic Mechanisms and Control Strategies, Current and Future Perspectives

“…Selenium supplementation reduces the activation of the DON-induced Wnt/β-catenin pathway and partially reverses cell damage. 73 Therefore, the precise relationship between DON and Wnt/β-catenin is yet to be determined. The effect of DON on the Wnt/β-catenin signaling pathway needs to be explored further.…”

“…71,72 Although most studies have shown that DON inhibits Wnt/ β-catenin signaling pathway activity to exert toxic effects, another study has reported that exposure to DON (0.4 μg/ mL) can promote the activation of the Wnt/β-catenin pathway. 73 DON can induce cell damage, inhibit matrix synthesis, activate Wnt/β-catenin signaling, and increase the catabolism of cells, promoting the development of the Kashin− Beck disease. Selenium supplementation reduces the activation of the DON-induced Wnt/β-catenin pathway and partially reverses cell damage.…”

Protective and detoxifying effects conferred by selenium against mycotoxins and livestock viruses: A review

“…These fungal secondary metabolites, which include ochratoxin A (OTA), deoxynivalenol (DON), fumonisin B (FBs), T-2 toxin, zearalenone (ZEA, ZEN), and aflatoxin B1 (AFB1), can contaminate grains anywhere between their growing period and their processing, with exposure to the mycotoxins resulting in acute and chronic poisoning in both animals and humans. In this context, studies have shown that selenium (Se), a microelement first discovered in 1817 (1), is effective at reducing the toxicity of mycotoxins (2)(3)(4). This element can exist as part of organic and inorganic compounds, with Se-methylselenocysteine (MSC), seleno-Lmethionine (SLM), and selenocysteine (5) representing the main organic types while selenades (e.g., H 2 Se, HSe − ), in contrast, selenates (e.g., SeO 2− 4 , HSeO − 4 , H 2 SeO 4 ) and selenites (e.g., SeO 2− 3 , HSeO − 3 , H 2 SeO 3 ) represent major inorganic ones (6).…”