Shinohara Masahiro, Takayanagi Hiroshi
Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549, Japan.
Curr Osteoporos Rep. 2007 Jun;5(2):67-72. doi: 10.1007/s11914-007-0005-1.
Osteoclasts are cells of monocyte/macrophage origin that degrade bone matrix. Receptor activator of NF-kappaB ligand (RANKL) induces osteoclast differentiation in the presence of macrophage colony-stimulating factor. RANKL activates the tumor necrosis factor receptor-associated factor 6, c-Fos, and calcium signaling pathways, all of which are indispensable for the induction and activation of nuclear factor of activated T cells (NFAT) c1. NFATc1 is the master transcription factor for osteoclast differentiation, which regulates many osteoclast-specific genes. Multiple immunoglobulin-like receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adapters, Fc receptor common chi subunit (FcRgamma), and DNAX-activating protein (DAP) 12 mediate costimulatory signals for RANK, which activate calcium signaling through phospholipase Cgamma (PLCgamma). In addition to calcineurin-NFATc1, calcium signaling activates the CaMK-CREB (calcium/calmodulin activated kinase-cyclic AMP-response element binding protein) pathway, which also plays a critical role in osteoclastogenesis. This review summarizes recent advances in the study of signaling mechanisms of osteoclast differentiation.
破骨细胞是起源于单核细胞/巨噬细胞的细胞，可降解骨基质。核因子κB受体激活剂配体（RANKL）在巨噬细胞集落刺激因子存在的情况下诱导破骨细胞分化。RANKL激活肿瘤坏死因子受体相关因子6、c-Fos和钙信号通路，所有这些对于活化T细胞核因子（NFAT）c1的诱导和激活都是必不可少的。NFATc1是破骨细胞分化的主要转录因子，它调节许多破骨细胞特异性基因。与含有基于免疫受体酪氨酸的激活基序（ITAM）的衔接蛋白、Fc受体共同χ亚基（FcRγ）和DNAX激活蛋白（DAP）12相关的多种免疫球蛋白样受体介导RANK的共刺激信号，其通过磷脂酶Cγ（PLCγ）激活钙信号。除了钙调神经磷酸酶-NFATc1外，钙信号还激活CaMK-CREB（钙/钙调蛋白激活激酶-环磷酸腺苷反应元件结合蛋白）途径，该途径在破骨细胞生成中也起关键作用。本文综述了破骨细胞分化信号机制研究的最新进展。
