IGF-1 Facilitates Cartilage Reconstruction by Regulating PI3K/AKT, MAPK, and NF-kB Signaling in Rabbit Osteoarthritis.
IGF-1 Facilitates Cartilage Reconstruction by Regulating PI3K/AKT, MAPK, and NF-kB Signaling in Rabbit Osteoarthritis.
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DOI：
10.2147/jir.s316756
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发表时间：
2021
影响因子：
4.5
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Hossain MA;Adithan A;Alam MJ;Kopalli SR;Kim B;Kang CW;Hwang KC;Kim JH
骨关节炎（OA）的发病机制以关节退行性变为特征。促炎细胞因子白细胞介素（IL）-1β通过刺激特定信号通路如NF-κB、PI 3 K/Akt和MAPKs通路在OA的发病机制中起重要作用。生长因子在OA中的分解代谢作用可能被丝氨酸激活的病原体所抑制。本研究的目的是研究胰岛素样生长因子-1（IGF-1）对IL-1β诱导的体外和体内兔膝关节OA模型软骨细胞凋亡的潜在影响。在本研究中，通过IL-1β治疗软骨细胞中的OA，并通过从兔膝关节股骨髁去除软骨来治疗关节软骨破裂。IGF-1治疗后，免疫组织化学和qRT-PCR检测OA表达和基质金属蛋白酶（MMP）的变化。流式细胞仪检测OA细胞内活性氧（ROS）的产生。此外，用显微镜研究疾病进展，并使用组织学分析病理生理学变化。采用Western blot技术检测与疾病进展相关的NF-κB、PI 3 K/Akt和P38（MAPK）特异性通路。MMPs和各种凋亡标志物的表达在IGF-1以剂量依赖性方式施用后下调，而TIMP-1显著上调。结果表明，IL-1β处理软骨细胞和软骨骨关节炎后，细胞内ROS水平明显升高。以上结果表明，IGF-1通过抑制PI 3 K/Akt和MAPKs特异性途径保护NF-κB通路。此外，宏观和病理学研究表明，它具有软骨保护作用，通过形成透明软骨。我们的研究结果表明，IGF-1通过调节MAPK和PI 3 K/Akt信号通路抑制NF-κB信号传导，并通过抑制ROS产生防止细胞凋亡，从而对OA发病机制具有保护作用。
The pathogenesis of osteoarthritis (OA) is characterized by joint degeneration. The pro-inflammatory cytokine interleukin (IL)-1β plays a vital role in the pathogenesis of OA by stimulation of specific signaling pathways like NF-κB, PI3K/Akt, and MAPKs pathways. The catabolic role of growth factors in the OA may be inhibited cytokine-activated pathogen. The purpose of this study was to investigate the potential effects of insulin-like growth factor-1 (IGF-1) on IL-1β-induced apoptosis in rabbit chondrocytes in vitro and in an in vivo rabbit knee OA model. In the present study, the OA developed in chondrocyte with the treatment of IL-1β and articular cartilage ruptures by removal of cartilage from the rabbit knee femoral condyle. After IGF-1 treatment, immunohistochemistry and qRT-PCR were identified OA expression with changes in MMPs (matrix metalloproteinases). The production of ROS (intracellular reactive oxygen species) in the OA was detected by flow cytometry. Further, the disease progression was microscopically investigated and pathophysiological changes were analyzed using histology. The NF-κB, PI3K/Akt and P38 (MAPK) specific pathways that are associated with disease progression were also checked using the Western blot technique. The expression of MMPs and various apoptotic markers are down-regulated following administration of IGF-1 in a dose-dependent fashion while significantly up-regulation of TIMP-1. The results showed that higher levels of ROS were observed upon treatment of chondrocytes and chondral OA with IL-1β. Collectively, our results indicated that IGF-1 protected NF-κB pathway by suppression of PI3K/Akt and MAPKs specific pathways. Furthermore, the macroscopic and pathological investigation showed that it has a chondroprotective effect by the formation of hyaline cartilage. Our results indicate a protective effect of IGF-1 against OA pathogenesis by inhibition of NF-κB signaling via regulation of the MAPK and PI3K/Akt signaling pathways and prevention of apoptosis by suppression of ROS production.