TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis

作者：Chao Fang, Rui Zhong, Shuai Lu, Gang Yu, Zhilin Liu, Chengyuan Yan, Jingyu Gao, Yang Tang, Yingming Wang, Qichun Zhao, Xinzhe Feng · 发表于：International Journal of Biological Sciences · 年份：2024 · DOI：10.7150/ijbs.91519 · 被引用次数：113 · 研究领域：Inflammation biomarkers and pathways、Neuroinflammation and Neurodegeneration Mechanisms、Osteoarthritis Treatment and Mechanisms

Objective: Osteoarthritis (OA) is the most prominent chronic arthritic disease, affecting over 3 billion people globally.Synovial macrophages, as immune cells, play an essential role in cartilage damage in OA.Therefore, regulating macrophages is crucial for controlling the pathological changes in OA.Triggering receptor expressed on myeloid cells 2 (TREM2), as expressed on immune cell surfaces, such as macrophages and dendritic cells, has suppressed inflammation and regulated M2 macrophage polarization but demonstrated an unknown role in synovial macrophage polarization in OA.This study aimed to investigate TREM2 expression downregulation in OA mice macrophages.Furthermore, the expression trend of TREM2 was associated with polarization-related molecule expression in macrophages of OA mice.Results: We used TREM2 knockout (TREM2-KO) mice to observe that TREM2 deficiency significantly exacerbated the joint inflammation response in OA mice, thereby accelerating disease progression.Separating macrophages and chondrocytes from TREM2-KO mice and co-cultivating them significantly increased chondrocyte apoptosis and inhibited chondrocyte proliferation.Further, TREM2 deficiency also significantly enhanced phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway activation, increasing nuclear factor kappa light chain enhancer of activated B cells (NF-B) signaling and C-X-C Motif Chemokine Ligand 3 (CXCL3) expression.Furthermore, NF-B signaling pathway inhibition significantly suppressed...