Department of Orthopedic Surgery, The Third Hospital of Shijiazhuang, Shijiazhuang 050011, Hebei, P.R. China.
Department of Nursing, Hebei Province Eighth People’s Hospital, Shijiazhuang 050011, Hebei, P.R. China.
Aging (Albany NY). 2024 May 7;16(9):7915-7927. doi: 10.18632/aging.205793.
This research aimed to explore IL-21/miR-361-5p/MAP3K9 expression in shoulder arthritis and identify its regulatory pathways.
We established a rat shoulder arthritis model, then quantified IL21 and miR-361-5p in synovial fluid using ELISA and monitored the arthritis development. Additionally, IL21's effect on miR-361-5p levels in cultured human chondrocytes (HC-a) was assessed. Chondrocyte cell cycle status and apoptosis were measured via flow cytometry. Interactions between miR-361-5p and MAP3K9 were confirmed through dual-luciferase reporting and bioinformatic scrutiny. Protein levels of MAP3K9, p-ERK1/2, p-NF-κB, MMP1, and MMP9 were analyzed by Western blots.
IL21 levels were elevated, while miR-361-5p was reduced in the synovial fluid from arthritic rats compared to healthy rats. IL21 was shown to suppress miR-361-5p in chondrocytes leading to hindered cell proliferation and increased apoptosis. Western blots indicated that miR-361-5p curbed MAP3K9 expression, reducing MMP activity by attenuating the ERK1/2/NF-κB pathway in chondrocytes.
IL21 upregulation and miR-361-5p downregulation characterize shoulder arthritis, resulting in MAP3K9 overexpression. This chain of molecular events boosts MMP expression in chondrocytes and exacerbates the condition's progression.
本研究旨在探讨白细胞介素 21（IL-21）/miR-361-5p/MAP3K9 在肩关节炎中的表达情况，并鉴定其调控途径。
我们建立了大鼠肩关节炎模型，然后使用 ELISA 定量检测滑液中的 IL21 和 miR-361-5p，并监测关节炎的发展。此外，还评估了 IL21 对培养的人软骨细胞（HC-a）中 miR-361-5p 水平的影响。通过流式细胞术测量软骨细胞的细胞周期状态和凋亡。通过双荧光素酶报告和生物信息学分析证实 miR-361-5p 与 MAP3K9 之间的相互作用。通过 Western blot 分析 MAP3K9、p-ERK1/2、p-NF-κB、MMP1 和 MMP9 的蛋白水平。
与健康大鼠相比，关节炎大鼠的滑液中 IL21 水平升高，而 miR-361-5p 水平降低。IL21 被证明可在软骨细胞中抑制 miR-361-5p，导致细胞增殖受阻和凋亡增加。Western blot 表明，miR-361-5p 通过抑制 MAP3K9 的表达，降低 MMP 活性，从而减弱 ERK1/2/NF-κB 通路在软骨细胞中的活性。
肩关节炎的特征是 IL21 上调和 miR-361-5p 下调，导致 MAP3K9 过表达。这一连串的分子事件增加了软骨细胞中 MMP 的表达，从而加剧了病情的进展。
