Nakashima Tomoki, Takayanagi Hiroshi
Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan.
J Bone Miner Metab. 2009;27(5):519-29. doi: 10.1007/s00774-009-0089-z. Epub 2009 May 20.
Investigation into arthritis as well as the numerous bone phenotypes found in mice lacking immune-related genes has highlighted the importance of the dynamic interplay between the bone and immune systems. It has recently led to both the emergence and subsequent rapid evolution of the field of osteoimmunology. Receptor activator of nuclear factor-kappaB ligand (RANKL) stimulates osteoclastogenesis through the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which is well known as a crucial regulator of immunity. Studies on RANKL signaling revealed various immune-related genes which are involved in the regulation of osteoclastogenesis. Bone destruction in rheumatoid arthritis is caused by the enhanced activity of osteoclasts resulting from the activation of T cells. Here we describe our efforts to address the challenging question as to how abnormal T-cell activation mechanistically induces bone destruction. The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions, the elucidation of which will provide a scientific basis for future therapeutic approaches to diseases related to both the bone and immune systems.
对关节炎以及在缺乏免疫相关基因的小鼠中发现的众多骨表型的研究，凸显了骨骼与免疫系统之间动态相互作用的重要性。这一研究最近促使了骨免疫学领域的兴起及随后的快速发展。核因子κB受体活化因子配体（RANKL）通过活化T细胞核因子细胞质1（NFATc1）刺激破骨细胞生成，NFATc1是众所周知的免疫关键调节因子。对RANKL信号传导的研究揭示了多种参与破骨细胞生成调节的免疫相关基因。类风湿性关节炎中的骨破坏是由T细胞活化导致破骨细胞活性增强引起的。在此，我们描述了我们为解决一个具有挑战性的问题所做的努力，即异常的T细胞活化如何通过机制诱导骨破坏。骨免疫学的范围已扩展到涵盖广泛的分子和细胞相互作用，对其阐明将为未来针对与骨骼和免疫系统相关疾病的治疗方法提供科学依据。
