Sato Kojiro, Takayanagi Hiroshi
Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Japan.
Curr Opin Rheumatol. 2006 Jul;18(4):419-26. doi: 10.1097/01.bor.0000231912.24740.a5.
Osteoclasts are terminally differentiated cells of the monocyte/macrophage lineage that resorb bone matrix. Bone destruction in rheumatoid arthritis is mainly attributable to the abnormal activation of osteoclasts, and studies on activation of osteoclasts by the immune system have led to the new research field called osteoimmunology. This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems.
The T-cell-mediated regulation of osteoclast differentiation is dependent on cytokines and membrane-bound factors expressed by T cells. The cross-talk between receptor activator of nuclear factor-kappaB ligand and interferon-gamma has been shown to be crucial for the regulation of osteoclast formation in arthritic joints. Recent studies indicate that an increasing number of immunomodulatory factors are associated with the regulation of bone metabolism: nuclear factor of activated T cells c1 has been shown to be the key transcription factor for osteoclastogenesis, the activation of which requires calcium signaling induced by the immunoglobulin-like receptors.
New findings in osteoimmunology will be instrumental in the development of strategies for research into the treatment of various diseases afflicting the skeletal and immune systems.
破骨细胞是单核细胞/巨噬细胞谱系的终末分化细胞，可吸收骨基质。类风湿关节炎中的骨破坏主要归因于破骨细胞的异常激活，而关于免疫系统对破骨细胞激活的研究催生了名为骨免疫学的新研究领域。这个跨学科领域对于生物学研究以及与骨骼和免疫系统相关疾病的治疗都非常重要。
T细胞介导的破骨细胞分化调节依赖于T细胞表达的细胞因子和膜结合因子。核因子κB受体活化因子配体与干扰素-γ之间的相互作用已被证明对关节炎关节中破骨细胞形成的调节至关重要。最近的研究表明，越来越多的免疫调节因子与骨代谢调节相关：活化T细胞核因子c1已被证明是破骨细胞生成的关键转录因子，其激活需要免疫球蛋白样受体诱导的钙信号。
骨免疫学的新发现将有助于制定针对影响骨骼和免疫系统的各种疾病的治疗研究策略。
