PRMT1 通过 AKT/FOXO1 信号通路促进颞下颌关节骨关节炎中外细胞外基质的降解和软骨细胞的凋亡。
PRMT1 promotes extracellular matrix degradation and apoptosis of chondrocytes in temporomandibular joint osteoarthritis via the AKT/FOXO1 signaling pathway.
机构信息
Department of Periodontics, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming 650031, Yunnan Province, China; Yunnan Key Laboratory of Stomatology, Kunming 650500, Yunnan Province, China; The First Dental Clinic of the Affiliated Stomatology Hospital of Kunming Medical University, Kunming 650221, Yunnan Province, China.
Yunnan Key Laboratory of Stomatology, Kunming 650500, Yunnan Province, China; Department of Orthodontics, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming 650031, Yunnan Province, China.
出版信息
Int J Biochem Cell Biol. 2021 Dec;141:106112. doi: 10.1016/j.biocel.2021.106112. Epub 2021 Oct 27.
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disease characterized by extracellular matrix (ECM) degradation and chondrocyte apoptosis. The aim of this study was to investigate the role of PRMT1 in TMJOA pathogenesis and its underlying molecular mechanism. Compared to the control group, PRMT1 was highly expressed in IL-1β-treated chondrocytes and articular cartilage following MIA injection into rat TMJs. Furthermore, knocking down PRMT1 considerably inhibited ECM degradation and apoptosis induced by IL-1β. Mechanistic analyses further revealed that PRMT1 knockdown activated the PI3K/AKT signaling pathway and prevented FOXO1 from translocating to the nucleus. Moreover, an inhibitor of AKT (LY294002) rescued the effect of PRMT1 knockdown on IL-1β-induced ECM degradation and apoptosis, and AMI-1, a selective inhibitor of PRMT1, inhibited PRMT1 expression and reversed the pathological progress of TMJOA. Thus, our findings suggest that PRMT1 plays an essential role in ECM degradation and chondrocyte apoptosis in TMJOA via the AKT/FOXO1 signaling pathway.
颞下颌关节骨关节炎（TMJOA）是一种慢性退行性关节疾病，其特征为细胞外基质（ECM）降解和软骨细胞凋亡。本研究旨在探讨 PRMT1 在 TMJOA 发病机制中的作用及其潜在的分子机制。与对照组相比，在大鼠 TMJ 中注射 MIA 后，IL-1β 处理的软骨细胞和关节软骨中 PRMT1 的表达水平显著升高。此外，敲低 PRMT1 可显著抑制 IL-1β 诱导的 ECM 降解和凋亡。机制分析进一步表明，PRMT1 敲低激活了 PI3K/AKT 信号通路，并阻止 FOXO1 向核内易位。此外，AKT 抑制剂（LY294002）挽救了 PRMT1 敲低对 IL-1β 诱导的 ECM 降解和凋亡的作用，而 PRMT1 的选择性抑制剂 AMI-1 抑制了 PRMT1 的表达并逆转了 TMJOA 的病理进程。因此，我们的研究结果表明，PRMT1 通过 AKT/FOXO1 信号通路在 TMJOA 中的 ECM 降解和软骨细胞凋亡中发挥重要作用。
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