Osteoclast differentiation factor is a ligand for osteoprotegerin osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
Osteoclast differentiation factor is a ligand for osteoprotegerin osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
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DOI：
10.1073/pnas.95.7.3597
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发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Yasuda, H;Shima, N;Suda, T
破骨细胞是由单核/巨噬细胞系造血细胞分化而来的多核骨吸收细胞，破骨细胞样细胞（OCL）是脾细胞与成骨细胞或骨髓基质细胞在骨吸收因子存在下共同培养形成的，成骨细胞/基质细胞与破骨细胞祖细胞之间的细胞间相互作用是OCL形成的必要条件。我们纯化兰德分子克隆了破骨细胞生成抑制因子（OCIF），它与骨保护素（OPG）相同，OPG/OCIF是肿瘤坏死因子受体家族的分泌成员，通过中断细胞与细胞的相互作用来抑制破骨细胞生成，本文报道了从小鼠骨髓基质细胞的互补DNA文库中克隆OPG/OCIF配体的表达，发现该蛋白是膜相关肿瘤坏死因子配体家族的成员，并诱导破骨细胞祖细胞形成OCL，含有蛋白质胞外结构域的基因工程可溶性形式在不存在成骨细胞/基质细胞的情况下诱导脾细胞形成OCL，OPG/OCIF消除了蛋白质诱导的OCL形成，其基因在成骨细胞/基质细胞中的表达被骨吸收因子上调，我们得出结论，该膜结合蛋白是破骨细胞分化因子（ODF），其是一种长期寻找的配体，介导破骨细胞祖细胞向破骨细胞分化的必要信号。发现ODF与TRANCE/RANKL相同，其促进T细胞生长和树突状细胞功能，ODF似乎不仅在破骨细胞生成中而且在免疫系统中是重要的调节剂。
Osteoclasts, the multinucleated cells that resorb bone, develop from hematopoietic cells of monocyte/ macrophage lineage, Osteoclast-like cells (OCLs) are formed by coculturing spleen cells with osteoblasts or bone marrow stromal cells in the presence of bone-resorbing factors, The cell-to cell interaction between osteoblasts/stromal cells and osteoclast progenitors is essential for OCL formation, Recently, we purified rand molecularly cloned osteoclastogenesis-inhibitory factor (OCIF), which was identical to osteoprote-gerin (OPG), OPG/OCIF is a secreted member of the tumor necrosis factor receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction, Here we report the expression cloning of a ligand for OPG/OCIF from a complementary DNA library of mouse stromal cells, The protein was found to be a member of the membrane-associated tumor necrosis factor ligand family and induced OCL formation from osteoclast progenitors, A genetically engineered soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells, OPG/OCIF abolished the OCL formation induced by the protein, Expression of its gene in osteoblasts/stromal cells was up-regulated by bone-resorbing factors, We conclude that the membrane-bound protein is osteoclast differentiation factor (ODF), a long-sought ligand mediating an essential signal to osteoclast progenitors for their differentiation into osteoclasts. ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function, ODF seems to be an important regulator in not only osteoclastogenesis but also immune system.