Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Int J Mol Sci. 2022 Jan 27;23(3):1481. doi: 10.3390/ijms23031481.
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by inducing inflammatory reactions such as phagocytes and cytocidal systems activation. TNF-α also plays an important role in bone metabolism and is associated with inflammatory bone diseases. TNF-α binds to two cell surface receptors, the 55kDa TNF receptor-1 (TNFR1) and the 75kDa TNF receptor-2 (TNFR2). Bone is in a constant state of turnover; it is continuously degraded and built via the process of bone remodeling, which results from the regulated balance between bone-resorbing osteoclasts, bone-forming osteoblasts, and the mechanosensory cell type osteocytes. Precise interactions between these cells maintain skeletal homeostasis. Studies have shown that TNF-α affects bone-related cells via TNFRs. Signaling through either receptor results in different outcomes in different cell types as well as in the same cell type. This review summarizes and discusses current research on the TNF-α and TNFR interaction and its role in bone-related cells.
肿瘤坏死因子-α（TNF-α）是一种由巨噬细胞、单核细胞和 T 细胞表达的多效细胞因子，其表达由免疫系统触发，以响应病原体及其产物，如内毒素。TNF-α通过诱导吞噬细胞和细胞毒性系统的激活等炎症反应，在宿主防御中发挥重要作用。TNF-α还在骨代谢中发挥重要作用，并与炎症性骨病有关。TNF-α与两种细胞表面受体结合，即 55kDa TNF 受体-1（TNFR1）和 75kDa TNF 受体-2（TNFR2）。骨骼处于不断更新的状态；通过骨重建过程，即骨吸收破骨细胞、骨形成成骨细胞和机械敏感细胞类型骨细胞之间的调节平衡，不断降解和构建骨骼。这些细胞之间的精确相互作用维持着骨骼的内稳态。研究表明，TNF-α通过 TNFR 影响与骨骼相关的细胞。两种受体的信号转导在不同细胞类型以及同一细胞类型中产生不同的结果。这篇综述总结并讨论了目前关于 TNF-α和 TNFR 相互作用及其在与骨骼相关的细胞中的作用的研究。
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