Tendinopathy is a disabling musculoskeletal disease, the pathological process of which is tightly associated with inflammation. Spironolactone (SP) has been widely used as a diuretic in clinical practice. Recently, SP has shown anti-inflammatory features in several diseases. Tendon-derived stem cells (TDSCs), a subset cell type from tendon tissue possessing clonogenic capacity, play a vital role in the pathological process of tendinopathy. In the present study, the protective effect of SP on TDSCs was demonstrated under simulated tendinopathy conditions both in vitro and in vivo. SP contributed to the maintenance of TDSC-specific genes or proteins, while suppressing the interleukin- (IL-) 1β-induced overexpression of inflammation-mediated factors. Additionally, IL-1β-induced cellular senescence in TDSCs was inhibited, while autophagy was enhanced, as determined via β-galactosidase activity, western blot (WB), and quantitative real-time polymerase chain reaction analysis. With the aid of several emerging bioinformatics tools, the mitogen-activated protein kinase (MAPK) pathway likely participated in the effect of SP, which was further validated through WB analysis and the use of MAPK agonist. Immunofluorescence analysis and an NF-κB agonist were used to confirm the inhibitory effect of SP on IL-1β-induced activation of the NF-κB pathway. X-ray, immunofluorescence, immunohistochemistry, hematoxylin and eosin staining, histological grades, and Masson staining showed that SP ameliorated tendinopathy in an Achilles tenotomy (AT) rat model in vivo. This work elucidates the protective role of SP on the pathological process of tendinopathy both in vitro and in vivo, indicating a potential therapeutic strategy for tendinopathy treatment.

中文翻译：

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螺内酯通过 NF-κB/MAPK 途径调节大鼠肌腱干细胞的自噬，改善衰老和钙化


肌腱病是一种致残性肌肉骨骼疾病，其病理过程与炎症密切相关。螺内酯（SP）作为利尿剂广泛应用于临床。最近，SP在多种疾病中显示出抗炎作用。肌腱衍生干细胞（TDSC）是肌腱组织中具有克隆形成能力的细胞亚群，在肌腱病的病理过程中发挥着至关重要的作用。在本研究中，在体外和体内模拟肌腱病条件下证明了 SP 对 TDSC 的保护作用。 SP 有助于维持 TDSC 特异性基因或蛋白质，同时抑制白细胞介素 (IL-) 1 β诱导的炎症介导因子的过度表达。此外，通过β-半乳糖苷酶活性、蛋白质印迹 (WB) 和定量实时聚合酶链反应分析确定，TDSC 中 IL-1 β诱导的细胞衰老受到抑制，而自噬增强。借助几种新兴的生物信息学工具，丝裂原激活蛋白激酶（MAPK）途径可能参与了 SP 的作用，这通过 WB 分析和 MAPK 激动剂的使用得到了进一步验证。使用免疫荧光分析和 NF- κ B 激动剂来确认 SP 对 IL-1 β诱导的 NF- κ B 通路激活的抑制作用。 X 射线、免疫荧光、免疫组织化学、苏木精和伊红染色、组织学分级和 Masson 染色表明，SP 可改善跟腱切断术 (AT) 大鼠体内模型的肌腱病。 这项工作在体外和体内阐明了SP对肌腱病病理过程的保护作用，为肌腱病治疗提供了潜在的治疗策略。