Kong Y Y, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch E R, Van G, Nguyen L T, Ohashi P S, Lacey D L, Fish E, Boyle W J, Penninger J M
Amgen Institute, Toronto, Ontario, Canada.
Nature. 1999 Nov 18;402(6759):304-9. doi: 10.1038/46303.
Bone remodelling and bone loss are controlled by a balance between the tumour necrosis factor family molecule osteoprotegerin ligand (OPGL) and its decoy receptor osteoprotegerin (OPG). In addition, OPGL regulates lymph node organogenesis, lymphocyte development and interactions between T cells and dendritic cells in the immune system. The OPGL receptor, RANK, is expressed on chondrocytes, osteoclast precursors and mature osteoclasts. OPGL expression in T cells is induced by antigen receptor engagement, which suggests that activated T cells may influence bone metabolism through OPGL and RANK. Here we report that activated T cells can directly trigger osteoclastogenesis through OPGL. Systemic activation of T cells in vivo leads to an OPGL-mediated increase in osteoclastogenesis and bone loss. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe joint inflammation, bone and cartilage destruction and crippling, blocking of OPGL through osteoprotegerin treatment at the onset of disease prevents bone and cartilage destruction but not inflammation. These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology.
骨重塑和骨质流失由肿瘤坏死因子家族分子骨保护素配体（OPGL）与其诱饵受体骨保护素（OPG）之间的平衡所控制。此外，OPGL调节免疫系统中淋巴结的器官发生、淋巴细胞发育以及T细胞与树突状细胞之间的相互作用。OPGL受体RANK在软骨细胞、破骨细胞前体和成熟破骨细胞上表达。T细胞中OPGL的表达由抗原受体结合诱导，这表明活化的T细胞可能通过OPGL和RANK影响骨代谢。在此我们报告活化的T细胞可通过OPGL直接触发破骨细胞生成。体内T细胞的全身活化导致OPGL介导的破骨细胞生成增加和骨质流失。在以严重关节炎症、骨和软骨破坏以及致残为特征的大鼠佐剂性关节炎的T细胞依赖性模型中，在疾病发作时通过骨保护素治疗阻断OPGL可防止骨和软骨破坏，但不能防止炎症。这些结果表明全身和局部T细胞活化均可导致OPGL产生及随后的骨质流失，并且它们为T细胞作为骨生理学调节因子提供了一种新的范例。
