Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Cytokine. 2021 Aug;144:155559. doi: 10.1016/j.cyto.2021.155559. Epub 2021 May 11.
The discovery of cytokine tumor necrosis factor (TNF) in the 20th century revealed numerous secrets about organ development. In particular, the functions identified for the receptor activator of nuclear factor kappa-β (NF-κβ) ligand (also known as the RANKL/osteoprotegerin ligand (OPGL) or RANK ligand/TNFSF11) in the homeostasis of skeletal structure, function and regulation were not anticipated. Empirical evidence established the receptor-ligand interaction of RANKL with RANK in osteoclast formation. Reverse signaling of RANKL triggers NF-κβ for the degradation of β-catenin to inhibit bone formation. There is also evidence that RANKL modifies the behavior of other cells in the bone microenvironment, including osteoblasts, chondrocytes, endothelial cells and lymphocytes during normal (homeostatic) and diseased (osteoimmune) states. Two forms of RANKL, i.e., soluble and membrane-bound RANKL, are produced by bone cells. Even though soluble RANKL (sRANKL) and membrane-bound RANKL (mRANKL) both stimulate osteoclast formation in vitro, their biological roles are different. mRANKL triggers osteoclastogenesis by binding to RANK through cell-cell interaction; however, sRANKL released from osteogenic cells binds to RANK without cell-cell interaction. This review attempts to hypothesize how sRANKL functions biologically in bone and explore how this hypothesis might influence future research.
20 世纪细胞因子肿瘤坏死因子（TNF）的发现揭示了许多关于器官发育的秘密。特别是，核因子 kappa-β（NF-κβ）配体（也称为 RANKL/骨保护素配体（OPGL）或 RANK 配体/TNFSF11）受体激活剂在骨骼结构、功能和调节中的稳态中的功能是意料之外的。经验证据证实了 RANKL 与破骨细胞形成中的 RANK 的受体-配体相互作用。RANKL 的反向信号触发 NF-κβ 降解 β-连环蛋白以抑制骨形成。还有证据表明，RANKL 改变了骨微环境中其他细胞的行为，包括成骨细胞、软骨细胞、内皮细胞和淋巴细胞在正常（稳态）和疾病（骨免疫）状态下的行为。两种形式的 RANKL，即可溶性和膜结合的 RANKL，由骨细胞产生。尽管可溶性 RANKL（sRANKL）和膜结合的 RANKL（mRANKL）都能在体外刺激破骨细胞形成，但它们的生物学作用不同。mRANKL 通过细胞-细胞相互作用与 RANK 结合触发破骨细胞生成；然而，骨生成细胞释放的 sRANKL 与 RANK 结合而无需细胞-细胞相互作用。本文试图假设 sRANKL 在骨骼中如何具有生物学功能，并探讨这一假设如何影响未来的研究。
