PDF(Pubmed)
Abstract：
Tributyltin chloride (TBTC) is known to have effects and mechanisms in various diseases; however, whether TBTC is detrimental to joints and causes osteoarthritis (OA), as well as its underlying mechanism, has not yet been fully elucidated. The present study explored the effects of TBTC on rat chondrocytes, as well as on mouse OA. The toxicity of TBTC toward rat chondrocytes was detected using a lactate dehydrogenase (LDH) leakage assay and cell viability was evaluated using the Cell Counting Kit‑8 assay. The results showed that TBTC decreased the viability of rat chondrocytes and increased the LDH leakage rate in a concentration‑dependent manner. Moreover, compared with in the control group, TBTC increased the expression levels of interleukin (IL)‑1β, IL‑18, matrix metalloproteinase (MMP)‑1, MMP‑13, NLR family pyrin domain containing 3 (NLRP3), caspase‑1, PYD and CARD domain containing, and gasdermin D in chondrocytes. Furthermore, knockdown of NLRP3 reversed the TBTC‑induced increases in LDH leakage and NLRP3 inflammasome‑associated protein levels. In vivo, TBTC exacerbated cartilage tissue damage in mice from the OA group, as evidenced by the attenuation of safranin O staining. In conclusion, TBTC may aggravate OA in mice by promoting chondrocyte damage and inducing pyroptosis through the activation of NLRP3 and caspase‑1 signaling. The present study demonstrated that TBTC can cause significant damage to the articular cartilage; therefore, TBTC contamination should be strictly monitored.
摘要：
氯化三丁基锡（TBTC）已知在各种疾病中具有作用和机制；然而，TBTC是否对关节有害并导致骨关节炎（OA），以及它的潜在机制，尚未完全阐明。本研究探讨了TBTC对大鼠软骨细胞的影响，以及对鼠标OA。使用乳酸脱氢酶（LDH）泄漏测定法检测TBTC对大鼠软骨细胞的毒性，并使用细胞计数试剂盒-8测定法评估细胞活力。结果表明，TBTC以浓度依赖性方式降低了大鼠软骨细胞的活力，并增加了LDH的泄漏率。此外，与对照组相比，TBTC增加白细胞介素（IL）-1β的表达水平，IL‑18，基质金属蛋白酶（MMP）‑1，MMP‑13，NLR家族pyrin结构域包含3（NLRP3），caspase-1，PYD和CARD结构域，和软骨细胞中的gasderminD。此外，NLRP3敲低逆转了TBTC诱导的LDH渗漏和NLRP3炎性体相关蛋白水平的增加。在体内,TBTC加重OA组小鼠软骨组织损伤,番红O染色的减弱证明了这一点。总之,TBTC可能通过激活NLRP3和caspase-1信号促进软骨细胞损伤和诱导细胞凋亡而加重小鼠OA。本研究表明，TBTC可对关节软骨造成显著损伤；因此，应严格监测TBTC污染。
