Determination of three isoforms of the receptor activator of nuclear factor-κB ligand and their differential expression in bone and thymus
Determination of three isoforms of the receptor activator of nuclear factor-κB ligand and their differential expression in bone and thymus
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DOI：
10.1210/en.142.4.1419
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发表时间：
2001-04-01
期刊：
影响因子：
4.8
通讯作者：
Hirokawa, K
中科院分区：
文献类型：
--
作者：
Ikeda, T;Kasai, M;Hirokawa, K
已知核因子（NF）-kappaB配体受体激活剂[RANKL;也称为肿瘤坏死因子相关激活诱导的细胞因子、骨保护素配体和破骨细胞分化因子]与NF-kappaB受体激活剂（RANK）结合，不仅是破骨细胞生成的关键因子，也是淋巴细胞发育的调节因子。在这项研究中，我们发现了另外两种RANKL亚型。RANKL，2具有比原始RANKL（RANKL 1）更短的细胞内结构域，RANKL，3缺乏跨膜结构域，被认为是可溶性形式。在骨髓基质细胞系ST 2和前成骨细胞系MC 3 T3-E1中，检测到所有三种RANKL亚型，但RANKL 2的表达优先被1 α，25-二羟维生素D-3和地塞米松抑制。在年轻成人胸腺中，CD 4（-）CD 8（-）双阴性细胞对所有三种亚型均呈阳性，CD 4（+）CD 8（+）双阳性细胞对RANKL 1和RANKL 3呈阳性，但对RANKL 2呈阴性，CD 4（+）CD 8（-）和CD 4（-）CD 8（+）单阳性细胞对所有三种亚型均呈阳性。用每种RANKL亚型转染的NIH 3 T3细胞的免疫荧光分析表明，三种RANKL亚型被翻译，RANKL 2蛋白主要停留在内质网和高尔基体网络中。这些结果表明存在三种RANXL-RANK通路。多个RANKL-RANK通路的存在表明破骨细胞生成或T细胞分化的RANKL-RANK系统比以前认为的更复杂。
The receptor activator of nuclear factor (NF)-kappaB ligand [RANKL; also known as tumor necrosis factor-related activation-induced cytokine, osteoprotegerin ligand, and osteoclast differentiation factor] is known to bind with the receptor activator of NF-kappaB (RANK) and act not only as a key factor for osteoclastogenesis but also as a regulator of lymphocyte development. In this study, we found two additional isoforms of RANKL. RANKL, 2 has a shorter intracellular domain than the original RANKL (RANKL 1), and RANKL, 3 lacks a transmembrane domain and was thought to act as a soluble form. In the bone marrow stromal cell line ST2 and preosteoblastic cell line MC3T3-E1, all three RANKL isoforms were detected, but the expression of RANKL 2 was preferentially suppressed by treatment with 1 alpha ,25-dihydroxyvitamin D-3 and dexamethasone. In young adult thymus, CD4(-)CD8(-) double-negative cells were positive for all three isoforms, CD4(+)CD8(+) double-positive cells were positive for RANKL 1 and RANKL 3 but negative for RANKL 2, and CD4(+)CD8(-) and CD4(-)CD8(+) single-positive cells were positive for all three isoforms. Immunofluorescence analyses of NIH3T3 cells transfected with each RANKL isoform indicated that the three RANKL, isoforms were translated, and RANKL, 2 protein predominantly stayed in the endoplasmic reticulum and Golgi networks. These results indicate that there are three kinds of RANXL-RANK pathways. The presence of multiple RANKL-RANK pathways suggests a more complicated RANKL-RANK system for osteoclastogenesis or T cell differentiation than previously thought.