Takayanagi Hiroshi
Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, , Center of Excellence (COE) Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Japan.
Mod Rheumatol. 2005;15(4):225-31. doi: 10.1007/s10165-005-0398-6.
Research into the bone destruction associated with rheumatoid arthritis has highlighted the importance of the interplay of the immune and skeletal systems. Arthritic bone destruction is attributable to the defective control of osteoclastogenesis by T cells. We revealed that excessive expression of receptor activator of NF-kappaB ligand (RANKL) and a paucity of interferon-gamma underlie the enhanced osteoclastogenesis in arthritis. The interdisciplinary research field called osteoimmunology has attracted further attention after identification of a number of unexpected bone phenotypes in mice lacking immunomodulatory molecules. Accumulating evidence suggests that the immune and skeletal systems share not only cytokines but also various signaling molecules, transcription factors, and membrane receptors. Thus, bone turns out to be a dynamic tissue that is constantly renewed, where the immune system participates to a hitherto unexpected extent. This emerging field will be of great importance for a better understanding and treatment of rheumatic diseases.
对类风湿性关节炎相关骨破坏的研究凸显了免疫系统与骨骼系统相互作用的重要性。关节炎性骨破坏归因于T细胞对破骨细胞生成的控制缺陷。我们发现,核因子κB受体活化因子配体(RANKL)的过度表达和干扰素-γ的缺乏是关节炎中破骨细胞生成增强的基础。在缺乏免疫调节分子的小鼠中发现了许多意想不到的骨表型后,名为骨免疫学的跨学科研究领域受到了进一步关注。越来越多的证据表明,免疫系统和骨骼系统不仅共享细胞因子,还共享各种信号分子、转录因子和膜受体。因此,骨骼原来是一个不断更新的动态组织,免疫系统在其中发挥着迄今意想不到的作用。这一新兴领域对于更好地理解和治疗风湿性疾病将具有重要意义。