https://scholars.lib.ntu.edu.tw/handle/123456789/627517
標題: | Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging | 作者: | Chung, Yao-Pang TE-I WENG DING-CHENG CHAN RONG-SEN YANG SHING-HWA LIU |
關鍵字: | Aging; Human chondrocytes; Mouse articular cartilage; Senescence; Tributyltin | 公開日期: | 二月-2023 | 出版社: | SPRINGER HEIDELBERG | 卷: | 97 | 期: | 2 | 起(迄)頁: | 547-559 | 來源出版物: | Archives of Toxicology | 摘要: | Tributyltin (TBT) is known as an endocrine-disrupting chemical. This study investigated the effects and possible mechanisms of TBT exposure on inducing human articular chondrocyte senescence in vitro at the human-relevant concentrations of 0.01-0.5 μM and mouse articular cartilage aging in vivo at the doses of 5 and 25 μg/kg/day, which were 5 times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively. TBT significantly increased the senescence-associated β-galactosidase activity and the protein expression levels of senescence markers p16, p53, and p21 in chondrocytes. TBT induced the protein phosphorylation of both p38 and JNK mitogen-activated protein kinases in which the JNK signaling was a main pathway to be involved in TBT-induced chondrocyte senescence. The phosphorylation of both ataxia-telangiectasia mutated (ATM) and histone protein H2AX (termed γH2AX) was also significantly increased in TBT-treated chondrocytes. ATM inhibitor significantly inhibited the protein expression levels of γH2AX, phosphorylated p38, phosphorylated JNK, p16, p53, and p21. TBT significantly stimulated the mRNA expression of senescence-associated secretory phenotype (SASP)-related factors, including IL-1β, TGF-β, TNF-α, ICAM-1, CCL2, and MMP13, and the protein expression of GATA4 and phosphorylated NF-κB-p65 in chondrocytes. Furthermore, TBT by oral gavage for 4 weeks in mice significantly enhanced the articular cartilage aging and abrasion. The protein expression of phosphorylated p38, phosphorylated JNK, GATA4, and phosphorylated NF-κB-p65, and the mRNA expression of SASP-related factors were enhanced in the mouse cartilages. These results suggest that TBT exposure can trigger human chondrocyte senescence in vitro and accelerating mouse articular cartilage aging in vivo. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627517 | ISSN: | 0340-5761 | DOI: | 10.1007/s00204-022-03407-x |
顯示於: | 醫學系 |
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