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Abstract：
O-linked N-acetylglucosamine protein modification (O-GlcNAcylation) is a dynamic post-translational modification (PTM) involving the covalent binding of serine and/or threonine residues, which regulates bone cell homeostasis. Reactive oxygen species (ROS) are increased due to oxidative stress in various pathological contexts related to bone remodeling, such as osteoporosis, arthritis, and bone fracture. Autophagy serves as a scavenger for ROS within bone marrow-derived mesenchymal stem cells, osteoclasts, and osteoblasts. However, oxidative stress-induced autophagy is affected by the metabolic status, leading to unfavorable clinical outcomes. O-GlcNAcylation can regulate the autophagy process both directly and indirectly through oxidative stress-related signaling pathways, ultimately improving bone remodeling. The present interventions for the bone remodeling process often focus on promoting osteogenesis or inhibiting osteoclast absorption, ignoring the effect of PTM on the overall process of bone remodeling. This review explores how O-GlcNAcylation synergizes with autophagy to exert multiple regulatory effects on bone remodeling under oxidative stress stimulation, indicating the application of O-GlcNAcylation as a new molecular target in the field of bone remodeling.
摘要：
O-连接的N-乙酰葡糖胺蛋白修饰（O-GlcNAcylation）是一种动态的翻译后修饰（PTM），涉及丝氨酸和/或苏氨酸残基的共价结合，调节骨细胞稳态。活性氧（ROS）由于与骨重建相关的各种病理背景下的氧化应激而增加，比如骨质疏松症，关节炎,和骨折。自噬可作为骨髓间充质干细胞内ROS的清除剂，破骨细胞,和成骨细胞。然而,氧化应激诱导的自噬受代谢状态的影响，导致不利的临床结果。O-GlcNAcylation可以通过氧化应激相关信号通路直接和间接调节自噬过程,最终改善骨骼重塑。目前骨重建过程的干预措施通常集中在促进成骨或抑制破骨细胞吸收。忽略PTM对骨重建整个过程的影响。本文综述了O-GlcNAcylation如何与自噬协同作用对氧化应激刺激下的骨重建发挥多重调节作用。表明O-GlcNAcylation作为新的分子靶标在骨重建领域的应用。
