Mir-155-5p Regulates Macrophage M1 Polarization And Apoptosis In The Synovial Fluid Of Patients With Knee Osteoarthritis

EXPERIMENTAL AND THERAPEUTIC MEDICINE(2021)

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摘要
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-alpha) 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.
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关键词
knee osteoarthritis, synovial fluid, microRNA-155-5p, macrophages, apoptosis
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