化学
阿霉素
软骨细胞
分子生物学
阿格里坎
II型胶原
免疫印迹
流式细胞术
活性氧
肿瘤坏死因子α
癌症研究
软骨
生物
体外
免疫学
病理
医学
生物化学
骨关节炎
内科学
化疗
解剖
替代医学
基因
关节软骨
作者
Cheng-Hung Wu,Jiayi Luo,Yuanxin Liu,Jiannan Fan,Xianwen Shang,Riguang Liu,Chuan Ye,Jihong Yang,Hong Cao
标识
DOI:10.1016/j.ejps.2021.106013
摘要
Doxorubicin (DOX) is widely used as an effective chemotherapy agent in human cancer. Our study aimed to explore the specific mechanism of DOX in osteoarthritis (OA).A mouse OA model was established by destabilizing the medial meniscus (DMM), and the role of DOX was determined by intraperitoneally injecting 5 or 10 mg/kg DOX. The expression of collagen type-II (Col-2) was detected by immunohistochemistry staining, and the expression of plasma interleukin (IL)-6 (IL-6), IL-1beta (IL-1β), and tumor necrosis factor (TNF)-alpha (TNF-α) was evaluated by specific ELISA kits, and the expression of Sry-related HMG box 9 (SOX-9) was detected by western blot. Bone marrow mesenchymal stem cells (BMMSCs) were used to explore the mechanism of DOX in vitro. Reactive oxygen species (ROS) production was determined by flow cytometry. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. Chondrocyte differentiation was evaluated by Alcian blue staining assay. The expression of chondrocyte differentiation-related markers was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).DOX exposure exacerbated OA progression and inhibited chondrocyte differentiation of BMMSCs. DOX also increased ROS production in BMMSCs. Meanwhile, DOX further increased the elevation of plasma IL-6, IL-1β and TNF-α induced by DMM and obviously reduced the expression of chondrocyte differentiation-related markers, including collagen type II a1 (Col2A1), collagen type X alpha 1 (Col10A1), and aggrecan. Moreover, ROS scavengers NAC and MitoQ efficiently alleviated DOX toxicity, including ROS production and chondrocyte differentiation in BMMSCs.Our study revealed that DOX suppressed chondrocyte differentiation by stimulating ROS production, providing a novel theoretical strategy for the clinical treatment of OA caused by DOX.
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