Yunheng Zhang,1,* Maorong Liu,1,* Xuan Wang,1,* Nongchao Li,1,2 Xin Chang,1 Junkui Xu,1 Feng Tian,1 Xiaodong Wen,1 Cheng Liu,1 Yi Li1 

1Department of Foot and Ankle Surgery, Honghui Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2The Second Clinical Medical College of Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Li, Email footankle08@126.com Cheng Liu, Email 925980519@qq.com

Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: osteoarthritis, fucosylation, fucosyltransferase, molecular mechanism, notch pathway