School of Public Health, 12480Health Science Center of Xi'an Jiaotong University, and Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission of the People's Republic of China, and Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, Shaanxi, P.R China.
School of Nursing, Health Science Center, RINGGOLDID: 12480Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221075555. doi: 10.1177/09603271221075555.
T-2 toxin pre-disposes individuals to osteoarthritis, Kashin-Beck disease (KBD). The major pathological change associated with KBD is the degradation of the articular cartilage matrix. Herein, we investigated the key molecules that regulate T-2 toxin-mediated cartilage degradation. Potential KBD treatments were also investigated. Sprague Dawley rats were divided into the T-2 toxin group and the control group. The T-2 toxin group received 100 ng/g BW/day, whereas the control group received a similar dose of PBS. The expression of matrix metalloproteinase-13 (MMP-13) and TGF-β receptor I/II (TGF-βRI/II) was analyzed using immunohistochemical staining. C28/I2 chondrocytes were exposed to TGF-βRI/II binding inhibitor (GW788388) for 24 h before incubation in different T-2 toxin concentrations (0, 6, 12, and 24 ng/mL for 72 h). The expression of mRNA for TGF-βRI/II, MMP-13 and proteins for MMP-13, and Smad-2 in chondrocytes were analyzed using RT-PCR and western blot, respectively. Safranin O staining revealed that T-2 toxin treatment modulated the expression of articular cartilage matrix. On the other hand, T-2 toxin treatment sharply increased the expression of MMP-13, TGF-βRI, and TGF-βRII in the rat cartilages. Interestingly, blocking the TGF-βRs-smad 2 signaling pathway using GW788388 abrogated the effect of T-2 toxin on upregulating MMP-13 expression. The expression of MMP-13 in chondrocytes induced with T-2 toxin is regulated via the TGF-βRs signaling pathway. As such, inhibiting the expression of TGF-βRs is a potential KBD treatment.
T-2 毒素使个体易患骨关节炎和卡森-贝克病（KBD）。与 KBD 相关的主要病理变化是关节软骨基质的降解。在此，我们研究了调节 T-2 毒素介导的软骨降解的关键分子。还研究了潜在的 KBD 治疗方法。将 Sprague Dawley 大鼠分为 T-2 毒素组和对照组。T-2 毒素组每天接受 100ng/gBW，而对照组接受类似剂量的 PBS。使用免疫组织化学染色分析基质金属蛋白酶-13（MMP-13）和 TGF-β受体 I/II（TGF-βRI/II）的表达。在不同浓度的 T-2 毒素（0、6、12 和 24ng/mL，72h）孵育前，C28/I2 软骨细胞用 TGF-βRI/II 结合抑制剂（GW788388）孵育 24h。用 RT-PCR 和 Western blot 分别分析软骨细胞中 TGF-βRI/II、MMP-13 的 mRNA 表达和 MMP-13 蛋白和 Smad-2 蛋白。番红 O 染色显示 T-2 毒素处理调节关节软骨基质的表达。另一方面，T-2 毒素处理明显增加了大鼠软骨中 MMP-13、TGF-βRI 和 TGF-βRII 的表达。有趣的是，用 GW788388 阻断 TGF-βRs-smad 2 信号通路可消除 T-2 毒素对 MMP-13 表达的上调作用。T-2 毒素诱导的软骨细胞中 MMP-13 的表达受 TGF-βRs 信号通路调节。因此，抑制 TGF-βRs 的表达是一种潜在的 KBD 治疗方法。
