Aucubin suppresses TLR4 / NF ‐ κB signalling to shift macrophages toward M2 phenotype in glucocorticoid‐associated osteonecrosis of the femoral head

作者：Yue Chen, Guofeng Cui, Yan Cheng, Xue Zhang, Hong-Feng Sheng, Yidan Yang, Jiayi Guo, Youwen Liu, Bin Xu · 发表于：Journal of Cellular and Molecular Medicine · 年份：2024 · DOI：10.1111/jcmm.18583 · 被引用次数：11 · 研究领域：Bone and Joint Diseases、Bone health and treatments、Dermatological and COVID-19 studies

In this study, we investigated whether the ability of aucubin to mitigate the pathology of GONFH involves suppression of TLR4/NF-κB signalling and promotion of macrophage polarization to an M2 phenotype. In necrotic bone tissues from GONFH patients, we compared levels of pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages as well as levels of TLR4/NF-κB signalling. In a rat model of GONFH, we examined the effects of aucubin on these parameters. We further explored its mechanism of action in a cell culture model of M1 macrophages. Necrotic bone tissues from GONFH patients contained a significantly increased macrophage M1/M2 ratio, and higher levels of TLR4, MYD88 and NF-κB p65 than bone tissues from patients with hip osteoarthritis. Treating GONFH rats with aucubin mitigated bone necrosis and demineralization as well as destruction of trabecular bone and marrow in a dose-dependent manner, based on micro-computed tomography. These therapeutic effects were associated with a decrease in the overall number of macrophages, decrease in the proportion of M1 macrophages, increase in the proportion of M2 macrophages, and downregulation of TLR4, MYD88 and NF-κB p65. These effects in vivo were confirmed by treating cultures of M1 macrophage-like cells with aucubin. Aucubin mitigates bone pathology in GONFH by suppressing TLR4/NF-κB signalling to shift macrophages from a pro- to anti-inflammatory phenotype.