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, Bunkyo-ku, Tokyo, Japan.
J Periodontal Res. 2005 Aug;40(4):287-93. doi: 10.1111/j.1600-0765.2005.00814.x.
The metabolism of hard tissue is influenced by the immune system. Research into the bone destruction associated with inflammatory diseases such as periodontal disease and rheumatoid arthritis has highlighted the importance of the interplay of the immune and skeletal systems. This interdisciplinary research field, called 'osteoimmunology', has become increasingly important for each system by itself as well as the biology linking them. The history and recent progress of this field are reviewed.
'Osteoimmunology' was coined to describe the pioneering work on the T-cell regulation of osteoclastogenesis by the receptor activator of nuclear factor-kappaB ligand (RANKL) and interferon (IFN)-gamma. Accumulating evidence suggests that the immune and skeletal systems share not only cytokines but also various signaling molecules, transcription factors and membrane receptors. The contribution of T cells to the pathogenesis of inflammatory bone destruction is discussed, and our recent findings are summarized to illustrate how the osteoimmunological network functions.
RANKL is an osteoclastogenic cytokine that links bone and the immune system. Immunomodulatory cytokines such as IFNs also participate in the regulation of RANKL signaling and inflammatory bone loss. The transcription factor nuclear factor of activated T cells c1 (NFATc1) has been identified as a master switch regulator of osteoclastogenesis. In addition, immunoglobulin-like receptors are critically involved in bone homeostasis.
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 to a better understanding and treatment of diseases of the skeletal and immune systems, as well as to the fundamental biology underpinning both.
硬组织的新陈代谢受免疫系统影响。对与牙周病和类风湿性关节炎等炎症性疾病相关的骨破坏研究突显了免疫系统与骨骼系统相互作用的重要性。这个被称为“骨免疫学”的跨学科研究领域，对于每个系统自身以及连接它们的生物学而言都变得越来越重要。本文对该领域的历史和近期进展进行综述。
“骨免疫学”一词用于描述关于核因子-κB受体活化因子配体（RANKL）和干扰素（IFN）-γ对破骨细胞生成的T细胞调节的开创性研究。越来越多的证据表明，免疫系统与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。本文讨论了T细胞在炎症性骨破坏发病机制中的作用，并总结了我们最近的研究结果，以说明骨免疫学网络的功能。
RANKL是一种连接骨骼与免疫系统的破骨细胞生成细胞因子。免疫调节细胞因子如IFN也参与RANKL信号传导和炎症性骨丢失的调节。活化T细胞核因子c1（NFATc1）转录因子已被确定为破骨细胞生成的主要开关调节因子。此外，免疫球蛋白样受体在骨稳态中起关键作用。
事实证明，骨骼是一个不断更新的动态组织，免疫系统在其中的参与程度迄今出乎意料。这个新兴领域对于更好地理解和治疗骨骼与免疫系统疾病以及支撑这两个系统的基础生物学具有重要意义。
