PI3K/AKT/mTOR in synovial fluid extends the proinflammatory response of macrophage polarization in knee osteoarthritis
10.19405/j.cnki.issn1000-1492.2024.03.002
- VernacularTitle:滑膜液中PI3K/AKT/mTOR信号轴介导巨噬细胞极化对膝骨关节炎促炎反应的作用
- Author:
Zong JIANG
1
;
Tengxun GUO
;
Xiaoling YAO
;
Weiya LAN
;
Fang TANG
;
Wukai MA
;
Jia LIU
Author Information
1. 贵州中医药大学第二临床医学院,贵阳 550002
- Keywords:
knee osteoarthritis;
macrophage polarization;
M1/M2;
PI3K/AKT/mTOR signaling pathway;
synovi-al fluid;
inflammation
- From:
Acta Universitatis Medicinalis Anhui
2024;59(3):377-383
- CountryChina
- Language:Chinese
-
Abstract:
Objective Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA),this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression.Methods The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected,and the percentage of M1 macrophages(CD80,CD86)and M2 macrophages(CD163,CD206)in the synovial fluid(M1/M2 ratio)was measured to e-valuate the polarization of macrophage cytokines such as IL-1,IL-6,IL-10,and tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β Expression in KOA synovial fluid,and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K,AKT3,mTORC1,and inducible nitric oxide synthase(iONS)in KOA synovial fluid.Results Compared with the synovial fluid of normal individuals,the percentage of M1 macrophages(CD80,CD86)in KOA patients increased(P<0.01),and the M1/M2 ratio increased(P<0.001);The ex-pression of IL-1,IL-6,and TNF-α in the synovial fluid of the KOA group was also higher than that of the control group(P<0.01),while the expression of IL-10 and TGF-β in the KOA group was significantly reduced(P<0.01);The key proteins PI3K,AKT3,mTORC1,and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01).Conclusion In KOA synovial fluid,M1 macrophage polarization plays a dominant role,and the inflam-matory response mediated by M1 macrophage polarization may be the cause of synovitis.At the same time,the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato-ry response.
