Zhang Yunheng, Liu Maorong, Wang Xuan, Li Nongchao, Chang Xin, Xu Junkui, Tian Feng, Wen Xiaodong, Liu Cheng, Li Yi
Department of Foot and Ankle Surgery, Honghui Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
The Second Clinical Medical College of Shaanxi University of Chinese Medicine, Xianyang, People's Republic of China.
J Inflamm Res. 2025 Aug 18;18:11317-11334. doi: 10.2147/JIR.S520179. eCollection 2025.
Osteoarthritis is a chronic degenerative disease characterised by damage to articular cartilage and degradation of the chondrocyte matrix. It has been shown that inflammation occurs with a variety of protein glycosylation abnormalities, among which elevated levels of fucosylation is one of the characteristics of OA. Now, the relationship between fucosylation and OA is not clear. By summarizing, we infer that elevated levels of fucosylation may affect the course of OA, possibly through the Notch signalling pathway.
In in vitro experiments, we established a cellular inflammation model on a mature human chondrocyte cell line and intervened with the inhibitor SGN-2FF. The effect of decreased levels of fucosylation on chondrocyte apoptosis was observed by methods such as Calcein-AM/PI staining and Lectin blotting. By western bolt and immunofluorescence, it was verified that the decreased level of fucosylation could affect the activity of Notch signalling pathway and reduce the release of inflammatory factors, thus alleviating inflammation. In in vivo experiments, OA rats were treated by joint cavity injection of SGN-2FF, and the treatment status was assessed by ELISA and Micro-CT analysis.
We found abnormally elevated levels of fucosylation in a model of chondrocyte inflammation. Upon inhibition of fucosylation using SGN-2FF, there was a decrease in the expression of inflammation-related factors and a decrease in the number of apoptotic cells. With the decrease of fucosylation, the expression of activated Notch1 was significantly reduced, hindering the activation of Notch pathway and reducing the release of pro-inflammatory factors. Animal experiments showed that inhibition of fucoidan glycosylation could effectively reduce the expression of IL-6 and TNF-α, reduce cartilage damage and alleviate OA.
Inhibition of fucosylation can ameliorate chondrocyte inflammation and extracellular matrix degradation by decreasing Notch1 activity and down-regulating the expression of the Notch pathway, which can effectively alleviate the development of OA.
骨关节炎是一种慢性退行性疾病，其特征在于关节软骨损伤和软骨细胞基质降解。研究表明，多种蛋白质糖基化异常会引发炎症，其中岩藻糖基化水平升高是骨关节炎的特征之一。目前，岩藻糖基化与骨关节炎之间的关系尚不清楚。通过总结，我们推测岩藻糖基化水平升高可能会影响骨关节炎的病程，可能是通过Notch信号通路。
在体外实验中，我们在成熟的人软骨细胞系上建立了细胞炎症模型，并用抑制剂SGN-2FF进行干预。通过钙黄绿素-AM/PI染色和凝集素印迹等方法观察岩藻糖基化水平降低对软骨细胞凋亡的影响。通过蛋白质免疫印迹法和免疫荧光法，证实岩藻糖基化水平降低可影响Notch信号通路的活性，减少炎症因子的释放，从而减轻炎症。在体内实验中，通过关节腔注射SGN-2FF对骨关节炎大鼠进行治疗，并通过酶联免疫吸附测定法（ELISA）和显微计算机断层扫描（Micro-CT）分析评估治疗效果。
我们发现软骨细胞炎症模型中岩藻糖基化水平异常升高。使用SGN-2FF抑制岩藻糖基化后，炎症相关因子的表达减少，凋亡细胞数量减少。随着岩藻糖基化水平的降低，活化的Notch1表达显著降低，阻碍了Notch通路的激活，减少了促炎因子的释放。动物实验表明，抑制岩藻多糖糖基化可有效降低白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达，减少软骨损伤，减轻骨关节炎。
抑制岩藻糖基化可通过降低Notch1活性和下调Notch通路的表达来改善软骨细胞炎症和细胞外基质降解，从而有效缓解骨关节炎的发展。
