Identification of aberrant α-2,3 sialylation of cartilage associated with osteonecrosis of the femoral head based on integrated multi-omics analyses

基于整合多组学分析鉴定与股骨头坏死相关的软骨异常α-2,3唾液酸化

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Abstract

PURPOSE: Osteonecrosis of the femoral head (ONFH) is one of the most common and devastating articular cartilage diseases worldwide. The role of glycosylation in cartilage degeneration of ONFH is not yet fully understood. PATIENTS AND METHODS: The expression of glycogens in cartilage from ONFH patients was determined using our own whole-genome expression dataset. Moreover, the altered glycosylation associated with ONFH cartilage and methylprednisolone (MPS)-induced cell models was investigated by lectin microarrays. The synthesis of α-2,3 sialylation was repressed by silencing ST3GAL2, and the effect of α-2,3-sialylation on ONFH-associated molecular events was assessed. RESULTS: Our findings revealed that the expression of 18 glycogens (including ST3GAL2) were significantly changed in ONFH cartilage compared with those in fracture control cartilage. Moreover, the level of α-2,3 sialylation, which is catalyzed by ST3GAL2, was significantly increased in ONFH cartilage and cell models compared to their corresponding controls. Silencing the expression of ST3GAL2 not only reduced the level of α-2,3 sialylation but also suppressed the expression of proinflammatory cytokines, reduced apoptosis-related proteins, and inactivated the NF-κB signaling pathway. CONCLUSION: Our study highlighted the important role of α-2,3 sialylation in the development of ONFH, providing valuable insights into the molecular mechanisms underlying the pathogenesis of ONFH.

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