Zhang Hua, Li Jie, Xiang Xiaobing, Zhou Bengen, Zhao Changqing, Wei Qiushi, Sun Youqiang, Chen Jianfa, Lai Boyong, Luo Zequan, Li Aihua
Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Bone Joint Res. 2021 Nov;10(11):704-713. doi: 10.1302/2046-3758.1011.BJR-2020-0242.R4.
Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.
OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot.
Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro.
Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: 2021;10(11):704-713.
叔丁基对苯二酚（tBHQ）已被确定为人类神经干细胞氧化应激诱导损伤和细胞凋亡的抑制剂。然而，tBHQ在骨关节炎（OA）中的作用尚不清楚。本研究旨在探讨tBHQ在OA中的作用。
通过内侧半月板不稳定（DMM）诱导OA动物模型。将不同浓度的tBHQ（25和50mg/kg）腹腔注射到10周龄雌性小鼠体内。从小鼠关节软骨中分离软骨细胞，用5ng/ml脂多糖（LPS）或10ng/ml白细胞介素1β（IL-1β）处理24小时，然后用不同浓度的tBHQ（10、20和40μM）处理12小时。检测血液中丙二醛（MDA）和超氧化物歧化酶（SOD）的表达水平。使用酶联免疫吸附测定（ELISA）试剂盒检测血浆中白细胞介素6（IL-6）、IL-1β和肿瘤坏死因子α（TNF-α）瘦素的表达水平。通过蛋白质印迹法检测活化B细胞核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路蛋白以及巨噬细胞极化相关标志物的表达。
叔丁基对苯二酚在体内显著减轻了DMM诱导小鼠的软骨破坏。它在体外显示出抑制IL-1β诱导的软骨细胞凋亡、炎症和分化缺陷的明确证据。同时，tBHQ在体外抑制LPS诱导的NF-κB和MAPK信号通路激活，也抑制LPS诱导的活性氧产生和巨噬细胞极化。
综上所述，tBHQ可能是预防OA发展的潜在治疗策略。引用本文：2021；10（11）：704-713。
