Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, China.
Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, China.
Biochem Biophys Res Commun. 2022 Dec 20;635:267-276. doi: 10.1016/j.bbrc.2022.10.059. Epub 2022 Oct 19.
Osteoarthritis, a prevalent orthopedic disease, can affect the elderly and causes impairment. The degradation and aberrant homeostasis of cartilage extracellular matrix figure pivotally in the progression of osteoarthritis. Thioredoxin systems plays a role in a wide range of biological processes, including cell proliferation, apoptosis, and oxidative stress. The present study aimed to investigate the unique function and underlying pathophysiological mechanism of TXNRD1 in chondrocytes. An upregulated expression of TXNRD1 was observed in the articular cartilage of osteoarthritis patients compared with normal articular cartilage. Furthermore, in vitro experiments showed that the expression of TXNRD1 was also abnormally increased in IL-1β-induced primary mouse chondrocytes. Silencing TXNRD1 using siRNA in chondrocytes could effectively inhibit the expression of ADAMTS5 and MMP13, and enhance the expression of COL2A1 and SOX9. The same was true for auranofin, an inhibitor of TXNRD1. This phenomenon indicated that inhibition of TXNRD1 attenuated il-1β-induced metabolic imbalance of extracellular matrix (ECM) and the progression of chondrocyte osteoarthritis. Further mechanism analysis revealed that the activation of Nrf2 signaling pathway and the expression of heme oxygenase-1 (HO-1) were increased upon TXNRD1 inhibition. Furthermore, auranofin was found to attenuate DMM-induced osteoarthritis progression in vivo. Therefore, the pharmacological downregulation of TXNRD1 may provide an effective novel therapy for OA.
骨关节炎是一种常见的骨科疾病，可影响老年人并导致功能障碍。软骨细胞外基质的降解和异常的动态平衡在骨关节炎的进展中起着关键作用。硫氧还蛋白系统在广泛的生物学过程中发挥作用，包括细胞增殖、凋亡和氧化应激。本研究旨在探讨 TXNRD1 在软骨细胞中的独特功能和潜在的病理生理机制。与正常关节软骨相比，骨关节炎患者的关节软骨中 TXNRD1 的表达上调。此外，体外实验表明，IL-1β诱导的原代小鼠软骨细胞中 TXNRD1 的表达也异常增加。在软骨细胞中使用 siRNA 沉默 TXNRD1 可有效抑制 ADAMTS5 和 MMP13 的表达，增强 COL2A1 和 SOX9 的表达。TXNRD1 的抑制剂金诺芬也是如此。这一现象表明，抑制 TXNRD1 可减轻 il-1β 诱导的细胞外基质（ECM）代谢失衡和软骨细胞骨关节炎的进展。进一步的机制分析表明，TXNRD1 抑制后 Nrf2 信号通路的激活和血红素加氧酶-1（HO-1）的表达增加。此外，还发现金诺芬可减轻 DMM 诱导的体内骨关节炎进展。因此，TXNRD1 的药理学下调可能为 OA 提供一种有效的新型治疗方法。
