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首页> 外文期刊>Drug Design, Development and Therapy >Cordycepin Alleviates Anterior Cruciate Ligament Transection (ACLT)-Induced Knee Osteoarthritis Through Regulating TGF-β Activity and Autophagy
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Cordycepin Alleviates Anterior Cruciate Ligament Transection (ACLT)-Induced Knee Osteoarthritis Through Regulating TGF-β Activity and Autophagy

机译：通过调节TGF-β活性和自噬，肠道蛋白减轻了前曲韧带横截面（ACLT）诱导的膝关节骨关节炎

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Introduction: Osteoarthritis is the most prevalent articular disease in the elderly. We aimed to explore the role of cordycepin (COR) in the progression and development of osteoarthritis and its correlation with TGF-β activity and autophagy. Methods: Sprague Dawley rats were induced by anterior cruciate ligament transection (ACLT) to establish knee osteoarthritis model. To investigate the role of COR in knee osteoarthritis, rats were injected with 5, 10, and 20 mg/kg of COR before joint surgery. After surgery, paw withdrawal mechanical threshold (PWMT) was performed. HE staining and Alcian blue staining were carried out to detect cartilage damage. ELISA was used to detect the level of TGFβ in the serum. Protein expression was analyzed by Western blotting. Results: In this study, we found that the PWMT of rats with osteoarthritis induced by ACLT was decreased significantly, accompanied by obvious histological and cartilage damage. After different doses of COR treatment, the PWMT of osteoarthritis rats induced by ACLT was increased in a dose-dependent manner. In addition, compared with the control group, COR treatment also reversed the effect of ACLT on cartilage injury in rats. Furthermore, the level of TGF-β in serum of ACLT rats was increased significantly, which may be related to the overexpression of TGF-β R1. However, the increase of serum TGF-β level in ACLT rats was reversed by COR treatment in a dose-dependent manner. It is worth noting that TGF-β overexpression reduced the proportion of autophagy-related protein LC3-II/I, thus inhibiting autophagy. In order to further confirm the effect of TGF-β on autophagy, TGF-β was overexpressed or the autophagy inhibitor 3-MA was applied. The results showed that TGF-β overexpression and 3-MA treatment reversed the effect of COR on autophagy. Conclusion: In summary, our findings declared that COR alleviated ACLT-induced osteoarthritis pain and cartilage damage by inhibiting TGF-β activity and inducing autophagy in rat model with knee osteoarthritis.
机译：介绍：骨关节炎是老年人中最普遍的关节疾病。我们的目标是探讨冬虫夏宾（Cor）在骨关节炎的进展和发展中的作用及其与TGF-β活性和自噬的相关性。方法：通过前十字韧带横截面（ACLT）诱导Sprague Dawley大鼠，以建立膝关节骨关节炎模型。为了探讨Cor在膝关节骨关节炎的作用，在关节手术前注射5,10和20mg / kg的糖。手术后，进行爪子取出机械阈值（PWMT）。他进行了染色和阿尔西亚蓝染色以检测软骨损伤。 ELISA用于检测血清中TGFβ的水平。通过蛋白质印迹分析蛋白质表达。结果：在本研究中，我们发现，ACLT诱导的骨关节炎的大鼠PWMT显着降低，伴有明显的组织学和软骨损伤。在不同剂量的Cor治疗后，ACLT诱导的骨关节炎大鼠的PWMT以剂量依赖性方式增加。此外，与对照组相比，Cor治疗还逆转了ACLT对大鼠软骨损伤的影响。此外，ACLT大鼠血清中TGF-β的水平显着增加，这可能与TGF-βR1的过度表达有关。然而，ACLT大鼠血清TGF-β水平的增加以剂量依赖性方式逆转。值得注意的是，TGF-β过度表达降低了与自噬相关蛋白LC3-II / I的比例，从而抑制了自噬。为了进一步证实TGF-β对自噬的影响，TGF-β过表达或施加自噬抑制剂3-MA。结果表明，TGF-β过度表达和3-MA治疗逆转了COR对自噬的作用。结论：总之，我们的调查结果宣布通过抑制TGF-β活性和肿瘤骨关节炎诱导大鼠模型的诱导症患者诱导的骨关节炎疼痛和软骨损伤。

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