OGT-induced O-GlcNAcylation of NEK7 protein aggravates osteoarthritis progression by enhancing NEK7/NLRP3 axis

Autor: Chunlei He, Qiang Wu, Zhaogan Zeng, Yadong Yang, Huabin He, Meiyu Hu, Sheng Liu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Autoimmunity, Vol 57, Iss 1 (2024)
Druh dokumentu: article
ISSN: 08916934
1607-842X
0891-6934
DOI: 10.1080/08916934.2024.2319202
Popis: AbstractBackgrounds The role of O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) has been reported in multiple human diseases. However, its specific functions in osteoarthritis (OA) progression remain undetermined.Objective This study focused on the target proteins of OGT-induced O-GlcNAcylation in OA and the specific functional mechanism.Methods The levels of total O-GlcNAc and OGT were measured in both in vitro and in vivo OA models using western blot. The effects of OGT knockout on OA progression were detected through Safranin O staining, immunohistochemical staining and OARSI score evaluation. The effects of OGT silencing on LPS-induced chondrocyte injury were assessed by performing loss-of function assays. Co-immunoprecipitation (co-IP) was conducted to verify the effect of OGT-induced O-GlcNAcylation on the interaction between NEK7 and NLRP3. The role of OGT in modulating the O-GlcNAcylation and phosphorylation levels of NEK7 was analysed using western blot.Results The OGT-indued O-GlcNAcylation level was increased in both in vitro and in vivo OA models. Knockout of OGT mitigated OA progression in model mice. Additionally, silencing of OGT suppressed LPS-induced chondrocyte pyroptosis. Moreover, silencing of OGT inhibited the O-GlcNAcylation and enhanced the phosphorylation of NEK7 at S260 site, thereby blocking the binding of NEK7 with NLRP3.Conclusion OGT-induced NEK7 O-GlcNAcylation promotes OA progression by promoting chondrocyte pyroptosis via the suppressing interaction between NEK7 and NLRP3.
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