Wang Ximeng, Zhang Yuxuan, Lin Zhidi, Wang Hongli, Xu Guangyu, Ma Xiaosheng
Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai, China.
Bone Joint Res. 2025 May 9;14(5):420-433. doi: 10.1302/2046-3758.145.BJR-2024-0259.R2.
Osteoporosis a is a metabolic bone disease caused by an imbalance in bone homeostasis, which is regulated by osteoblasts and osteoclasts. Protein palmitoylation modification is a post-translational modification that affects protein function, localization, and targeting by attaching palmitoyl groups to specific amino acid residues of proteins. Recent studies have shown that protein palmitoylation is involved in the regulation of osteoclast overproduction, osteoblast migration, osteogenic differentiation, dysfunctional autophagy, and endocrine hormone membrane receptors in osteoporosis. Exactly to what extent palmitoylation modifications can regulate osteoporosis, and whether palmitoylation inhibition can delay osteoporosis, is a key question that needs to be investigated urgently. In this review, we observed that palmitoylation modifications act mainly through two target cells - osteoblasts and osteoclasts - and that the targets of palmitoylation modifications are focused on plasma membrane proteins or cytosolic proteins of the target cells, which tend to assume the role of receiving extracellular signals. We also noted that different palmitoyl transferases acting on different substrate proteins exert conflicting regulation of osteoblast function. We concluded that the regulation of osteocyte function, bone homeostasis, and osteoporosis by palmitoylation modifications is multidimensional, diverse, and interconnected. Perfecting the palmitoylation modification network can enhance our ability to utilize post-translational modifications to resist osteoporosis and lay the foundation for targeting palmitoyl transferases to treat osteoporosis in the future.
骨质疏松症是一种由骨内稳态失衡引起的代谢性骨病，骨内稳态由成骨细胞和破骨细胞调节。蛋白质棕榈酰化修饰是一种翻译后修饰，通过将棕榈酰基团连接到蛋白质的特定氨基酸残基上，影响蛋白质的功能、定位和靶向性。最近的研究表明，蛋白质棕榈酰化参与了骨质疏松症中破骨细胞过度生成、成骨细胞迁移、成骨分化、自噬功能障碍以及内分泌激素膜受体的调节。棕榈酰化修饰究竟能在多大程度上调节骨质疏松症，以及抑制棕榈酰化是否能延缓骨质疏松症，是一个亟待研究的关键问题。在这篇综述中，我们观察到棕榈酰化修饰主要通过两种靶细胞——成骨细胞和破骨细胞——起作用，并且棕榈酰化修饰的靶点集中在靶细胞的质膜蛋白或胞质蛋白上，这些蛋白往往承担接收细胞外信号的作用。我们还注意到，作用于不同底物蛋白的不同棕榈酰转移酶对成骨细胞功能发挥相互矛盾的调节作用。我们得出结论，棕榈酰化修饰对骨细胞功能、骨内稳态和骨质疏松症的调节是多维度、多样且相互关联的。完善棕榈酰化修饰网络可以增强我们利用翻译后修饰来抵抗骨质疏松症的能力，并为将来靶向棕榈酰转移酶治疗骨质疏松症奠定基础。
