Department of Orthopaedical Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Immunopharmacol Immunotoxicol. 2022 Aug;44(4):556-564. doi: 10.1080/08923973.2022.2065639. Epub 2022 Apr 20.
17β-Estradiol (E2) is an immune-regulatory agent with anti-inflammatory effects. However, it is still unknown whether E2 exerts pharmacological properties against Achilles tendinitis (AT). This study aims to investigate the effects of E2 on AT and its underlying mechanisms.
The established model of Achilles tendinitis was intraperitoneally injected with E2 (10, 20, or 30 μg/kg/d). After 8 weeks, biomechanical properties of the Achilles tendon were determined. Hydroxyproline content and tendon degeneration-related biomarkers were determined. The levels of inflammatory cytokines and apoptotic-related biomarkers in tendon tissues were determined. Furthermore, western blotting was determined to detect the expressions of ER-α and the PI3K/Akt pathway in tendon tissues.
E2 relieved AT-related symptoms in a dose-dependent manner. E2 ameliorated tendon degeneration by regulating tendon degeneration-related biomarkers (e.g. collagen types I and III, Decorin (DCN), and tenascin-C). Besides, treatment with E2 suppressed inflammatory cytokines and increased anti-inflammatory cytokines. Treatment with E2 also regulated cell apoptosis in tendon tissues. The underlying mechanism study revealed that treatment with E2 activated ER-α and upregulated the PI3K/Akt pathway.
The regulatory effects of E2 on inflammation and tendon degeneration in a rat model of AT were associated with the ER-α and the PI3K/Akt signaling pathways.
17β-雌二醇（E2）是一种具有抗炎作用的免疫调节剂。然而，E2 是否对跟腱炎（AT）具有药理作用仍不清楚。本研究旨在探讨 E2 对 AT 的作用及其潜在机制。
采用腹腔注射 E2（10、20 或 30μg/kg/d）建立跟腱炎模型。8 周后，测定跟腱的生物力学特性。测定羟脯氨酸含量和腱退变相关标志物。测定腱组织中炎症细胞因子和凋亡相关标志物的水平。此外，采用 Western blot 法检测腱组织中 ER-α 和 PI3K/Akt 通路的表达。
E2 以剂量依赖的方式缓解 AT 相关症状。E2 通过调节腱退变相关标志物（如胶原 I 和 III、Decorin（DCN）和 tenascin-C）来改善腱退变。此外，E2 治疗抑制了炎症细胞因子的产生并增加了抗炎细胞因子的水平。E2 治疗还调节了腱组织中的细胞凋亡。机制研究表明，E2 治疗通过激活 ER-α 并上调 PI3K/Akt 通路发挥作用。
E2 对 AT 大鼠模型中炎症和腱退变的调节作用与 ER-α 和 PI3K/Akt 信号通路有关。
