Hydroquinone, a cigarette smoke compound, affects cartilage homeostasis through activation of the aryl hydrocarbon receptor pathway
Hydroquinone, a cigarette smoke compound, affects cartilage homeostasis through activation of the aryl hydrocarbon receptor pathway
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DOI：
10.1101/2022.04.25.489372
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发表时间：
2022-04
期刊：
影响因子：
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通讯作者：
C. Heluany;A. De Palma;N. Day;S. H. Poliselli Farsky;Giovana Nalesso
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文献类型：
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作者：
C. Heluany;A. De Palma;N. Day;S. H. Poliselli Farsky;Giovana Nalesso
暴露于香烟烟雾已被证明对人体健康的各个方面都有不利影响。越来越多的证据表明吸烟与关节组织的退化有关。然而，香烟烟雾中不同成分引起的毒性机制尚未完全阐明。我们先前已经表明，暴露于氢醌（HQ），一种存在于香烟烟雾中的促氧化剂化学物质，可以通过激活芳烃受体（AhR）途径促进类风湿性关节炎小鼠模型中的关节组织降解。骨关节炎（OA）是一种慢性衰弱性关节疾病，其特征是关节软骨的进行性退化，其发病和进展也与吸烟有关。在这项工作中，我们的目的是研究HQ暴露对关节软骨细胞的影响，以及它如何影响软骨稳态。在存在或不存在IL-1β预刺激的情况下，在暴露于HQ的原代关节软骨细胞中定量细胞活力、基因表达、氧化应激和炎症参数。HQ刺激下调表型标记基因，如SOX-9和Col 2a 1，而上调分解代谢酶MMP-3和ADAMTS 5的表达。HQ还促进氧化应激和降低蛋白多糖含量。HQ加重了由IL-1β共刺激介导的促炎作用。最后，我们发现，HQ的退化作用介导的AhR的激活。总之，我们的研究结果解决了HQ对关节软骨健康的有害影响，为关节疾病发病的环境污染物的毒性机制提供了新的证据。
Exposure to cigarette smoke has a proven detrimental impact on different aspects of human health. Increasing evidences link smoking to degeneration of joint tissues. However, the toxic mechanisms elicited by the different components of cigarette smoke have not been fully elucidated yet. We have previously shown that exposure to hydroquinone (HQ), a pro-oxidant chemical present in cigarette smoke, can promote joint tissue degradation in murine models of rheumatoid arthritis through the activation of the aryl hydrocarbon receptor (AhR) pathway. Osteoarthritis (OA) is a chronic debilitating articular disease characterized by progressive degradation of the articular cartilage, whose onset and progression have also been associated with smoking. In this work we aimed to investigate the effect of HQ exposure on articular chondrocytes and how it affects cartilage homeostasis. Cell viability, gene expression, oxidative stress and inflammatory parameters were quantified in primary articular chondrocytes exposed to HQ in presence or absence of IL-1β pre-stimulation. HQ stimulation downregulated phenotypic markers genes such as SOX-9 and Col2a1, whereas upregulated the expression of the catabolic enzymes MMP-3 and ADAMTS5. HQ also promoted oxidative stress and reduced proteoglycan content. HQ exacerbated the pro-inflammatory effects mediated by the IL-1β co-stimulation. Finally, we showed that HQ-degenerative effects were mediated by the activation of AhR. Together, our findings address the harmful effects of HQ in the articular cartilage health, providing novel evidence surrounding the toxic mechanisms of environmental pollutants underlying the onset of articular diseases.