Action of RANKL and OPG for Osteoclastogenesis
Action of RANKL and OPG for Osteoclastogenesis
复制标题
DOI：
10.1615/critreveukargeneexpr.v19.i1.30
复制
发表时间：
2009-01-01
影响因子：
1.6
通讯作者：
Takahashi, Naoyuki
中科院分区：
文献类型：
--
作者：
Kobayashi, Yasuhiro;Udagawa, Nobuyuki;Takahashi, Naoyuki
破骨细胞从单核细胞-巨噬细胞谱系的造血细胞发育而来。建立了成骨细胞与造血细胞共培养体系，体外观察破骨细胞的生成。使用共培养系统的实验已经确立了成骨细胞在破骨细胞发生中至关重要的概念。破骨细胞分化的分子机制在过去的十年中取得了显著的进展，这主要是因为发现了NF-κ B配体受体激活因子（RANKL），一种破骨细胞生成的必需细胞因子。成骨细胞;表达RANKL以响应骨吸收因子。成骨细胞还产生骨保护素（OPG），一种RANKL的诱饵受体，其通过中断RANKL和RANK（RANKL的一种受体）之间的相互作用来抑制破骨细胞分化和功能。活化T细胞胞质核因子1（NFATc 1）作为RANKL诱导破骨细胞生成的主要转录因子的鉴定为破骨细胞分化的分子机制提供了重要的见解。免疫受体酪氨酸激活基序（ITAM）介导的信号作为破骨细胞生成中的共刺激信号的发现证实了成骨细胞在破骨细胞生成中发挥另一个重要作用。在人体中发现的RANK、OPG和RANKL突变可导致与预期骨骼异常相关的骨疾病。因此，RANKL/RANK/OPG轴现在被认为是破骨细胞分化和功能的中心调节因子。
Osteoclasts develop from hematopoietic cells of the monocyte-macrophage lineage. The coculture system of osteoblasts and hematopoietic cells was devised to examine osteoclastogenesis in vitro. Experiments using the coculture system have established the concept that osteoblasts are crucially involved in osteoclastogenesis. Remarkable progress has been achieved during the last decade in our understanding the molecular mechanism of osteoclast differentiation, largely because of the discovery of receptor activator of NF-kappa B ligand (RANKL), an essential cytokine for osteoclastogenesis. Osteoblast; express RANKL in response to bone-resorbing factors. Osteoblasts also produce osteoprotegerin (OPG), a decoy receptor for RANKL, which inhibits osteoclast differentiation and function by interrupting the interaction between RANKL and RANK, a receptor of RANKL. The identification of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) as a master transcription factor for RANKL-induced osteoclastogenesis has provided major insight into the molecular mechanism of osteoclast differentiation. The discovery of the immunoreceptor tyrosine-based activation motif (ITAM)-mediated signals as a costimulatory signal in osteoclastogenesis has confirmed that osteoblasts play another important role in osteoclastogenesis. Mutations of RANK, OPG, and RANKL found in humans cause bone diseases associated with expected skeletal abnormalities. Thus, the RANKL/RANK/OPG axis is now recognized as the central regulator of osteoclast differentiation and function.