Li Gui-Shi, Cui Lei, Wang Guang-Da
Department of Joint Orthopaedics, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
Department of Opthalmology Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
Exp Ther Med. 2021 Jan;21(1):68. doi: 10.3892/etm.2020.9500. Epub 2020 Nov 23.
Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases that affects millions of individuals worldwide. During OA, proinflammatory factors (including IL-1, IL-6, IL-17 and TNF-α) are released from chondrocytes and proliferating synoviocytes potentiate the proinflammatory microenvironment of the synovial fluid (SF). The altered SF microenvironment affects the infiltration, polarization and apoptosis of macrophages, though the underlying mechanisms are not completely understood. In the present study, the hypothesis that the knee synovial fluid of patients with knee osteoarthritis (KOA SF) promotes the polarization of peripheral blood mononuclear cell (PBMC)-derived M1 macrophages and inhibits PBMC-derived macrophage apoptosis was investigated. KOA SF increased PBMC-derived macrophage M1 polarization via the microRNA (miR)-155-5p/suppressor of cytokine signaling 1 signaling pathway. Caspase-3 (CASP3) was identified as a novel target of miR-155-5p, where KOA SF inhibited macrophage apoptosis via the miR-155-5p/CASP3 signaling pathway. The results suggested that the proinflammatory environment of KOA SF promoted macrophage M1 polarization and reduced macrophage apoptosis via miR-155-5p. The results provided a potential explanation for the increased number of M1 macrophages observed in KOA SF during OA. In addition, the present study suggested that miR-155-5p may serve as a potential therapeutic target for KOA.
骨关节炎（OA）是最常见的退行性关节疾病之一，影响着全球数百万人。在OA病程中，促炎因子（包括白细胞介素-1、白细胞介素-6、白细胞介素-17和肿瘤坏死因子-α）从软骨细胞中释放出来，增殖的滑膜细胞增强了滑液（SF）的促炎微环境。尽管其潜在机制尚未完全了解，但SF微环境的改变会影响巨噬细胞的浸润、极化和凋亡。在本研究中，探讨了膝骨关节炎患者的膝关节滑液（KOA SF）促进外周血单核细胞（PBMC）来源的M1巨噬细胞极化并抑制PBMC来源的巨噬细胞凋亡这一假说。KOA SF通过微小RNA（miR）-155-5p/细胞因子信号传导抑制因子1信号通路增加PBMC来源的巨噬细胞M1极化。半胱天冬酶-3（CASP3）被确定为miR-155-5p的一个新靶点，KOA SF通过miR-155-5p/CASP3信号通路抑制巨噬细胞凋亡。结果表明，KOA SF的促炎环境通过miR-155-5p促进巨噬细胞M1极化并减少巨噬细胞凋亡。这些结果为OA期间KOA SF中观察到的M1巨噬细胞数量增加提供了一个潜在的解释。此外，本研究表明miR-155-5p可能作为KOA的一个潜在治疗靶点。
