|Title:||Arsenic induces human chondrocyte senescence and accelerates rat articular cartilage aging||Authors:||Chung Y.-P.
|Issue Date:||2020||Journal Volume:||94||Journal Issue:||1||Start page/Pages:||89-101||Source:||Archives of Toxicology||Abstract:||
Arsenic-contaminated drinking water is known to be a serious human health problem. A previous epidemiological study has indicated that arsenic levels in blood were higher in arthritis patients compared to age-matched control subjects. Bone is known as an important arsenic store compartment in the body. Arsenic exposure has been suggested to promote senescence in human mesenchymal stem cells that may affect the balance of adipogenic and osteogenic differentiation. The toxicological effect and mechanism of arsenic exposure on articular chondrocytes still remain unclear. Here, we investigated the arsenic-induced senescence in cultured human articular chondrocytes and long-term arsenic-exposed rat articular cartilage. Arsenic trioxide (As2O3; 1–5?μM) significantly induced senescence in human articular chondrocytes by increasing senescence-associated β-galactosidase (SA-β-Gal) activity and protein expression of p16, p53, and p21. Arsenic induced the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) proteins. The inhibitors of p38 and JNK significantly reversed the arsenic-induced chondrocyte senescence. Arsenic could also trigger the induction of GATA4-NF-κB signaling and senescence-associated secretory phenotype (SASP) by increasing IL-1α, IL-1β, TGF-β, TNF-α, CCL2, PAI-1, and MMP13 mRNA expression. The increased cartilage senescence and abrasion were also observed in a rat model long-term treatment with arsenic (0.05 and 0.5?ppm) in drinking water for 36?weeks as compared to age-matched control rats. The phosphorylation of p38 and JNK and the induction of GATA4-NF-κB signaling and SASP were enhanced in the rat cartilages. Taken together, these findings suggest that arsenic exposure is capable of inducing chondrocyte senescence and accelerating rat articular cartilage aging and abrasion. ? 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
|URI:||https://scholars.lib.ntu.edu.tw/handle/123456789/508534||ISSN:||0340-5761||DOI:||10.1007/s00204-019-02607-2||SDG/Keyword:||arsenic; arsenic trioxide; beta galactosidase; collagenase 3; drinking water; immunoglobulin enhancer binding protein; interleukin 1alpha; interleukin 1beta; messenger RNA; protein p16; protein p21; protein p53; stress activated protein kinase; synaptophysin; transcription factor GATA 4; transforming growth factor beta; tumor necrosis factor; arsenic; GATA4 protein, human; immunoglobulin enhancer binding protein; mitogen activated protein kinase p38; transcription factor GATA 4; animal cell; animal experiment; animal model; Article; articular cartilage; cell aging; chondrocyte; controlled study; flow cytometry; human; human cell; human tissue; male; nonhuman; priority journal; protein expression; rat; signal transduction; animal; articular cartilage; cell aging; cell culture; chondrocyte; cytology; drug effect; MAPK signaling; metabolism; pathophysiology; toxicity testing; Wistar rat; Animals; Arsenic; Cartilage, Articular; Cells, Cultured; Cellular Senescence; Chondrocytes; GATA4 Transcription Factor; Humans; Male; MAP Kinase Signaling System; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats, Wistar; Toxicity Tests
|Appears in Collections:||法醫學科所|
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