Lineage-Committed Osteoclast Precursors Circulate in Blood and Settle Down Into Bone
Lineage-Committed Osteoclast Precursors Circulate in Blood and Settle Down Into Bone
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DOI：
10.1002/jbmr.490
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发表时间：
2011-12-01
影响因子：
6.2
通讯作者：
Takahashi, Naoyuki
中科院分区：
文献类型：
--
作者：
Muto, Akinori;Mizoguchi, Toshihide;Takahashi, Naoyuki
破骨细胞来源于单核细胞/巨噬细胞谱系，但对循环中的破骨细胞前体知之甚少。我们之前的研究表明，在骨表面检测到细胞周期阻滞的静态破骨细胞前体（QOPs）作为直接的破骨细胞前体。本研究表明，从小鼠骨髓和外周血中分离的NF-kappa B （RANK）阳性细胞的受体激活物具有小鼠QOPs的特征。rank阳性细胞表达不同水平的c-Fms（巨噬细胞集落刺激因子受体），但几乎不表达其他单核细胞/粒细胞标志物。rank阳性细胞不能发挥吞噬和增殖活性，只能分化为破骨细胞而不能分化为树突状细胞。为了鉴定循环QOPs，将含有骨形态发生蛋白-2 （BMP）的胶原圆盘植入小鼠体内，每天给药溴脱氧尿苷。bmp -2诱导异位骨的破骨细胞核多数呈溴脱氧尿嘧啶阴性。外周血中rank阳性细胞比F4/80（巨噬细胞标志物）阳性的巨噬细胞增殖更慢，寿命更长。将BMP盘和对照盘分别植入RANK配体缺陷小鼠，BMP盘中可见RANK阳性细胞，而对照组中未见。f4 /80阳性细胞分布于两椎间盘。给药FYT720（一种鞘氨醇1-磷酸激动剂）可促进rank阳性细胞从造血组织进入血液。这些结果表明，谱系决定的QOPs在血液中循环并在骨骼中沉淀。(C) 2011年美国骨与矿物研究学会。
Osteoclasts are derived from the monocyte/macrophage lineage, but little is known about osteoclast precursors in circulation. We previously showed that cell cycle-arrested quiescent osteoclast precursors (QOPs) were detected along bone surfaces as direct osteoclast precursors. Here we show that receptor activator of NF-kappa B (RANK)-positive cells isolated from bone marrow and peripheral blood possess characteristics of QOPs in mice. RANK-positive cells expressed c-Fms (receptors of macrophage colony-stimulating factor) at various levels, but scarcely expressed other monocyte/granulocyte markers. RANK-positive cells failed to exert phagocytic and proliferating activities, and differentiated into osteoclasts but not into dendritic cells. To identify circulating QOPs, collagen disks containing bone morphogenetic protein-2 (BMP disks) were implanted into mice, which were administered bromodeoxyuridine daily. Most nuclei of osteoclasts detected in BMP-2-induced ectopic bone were bromodeoxyuridine-negative. RANK-positive cells in peripheral blood proliferated more slowly and had a much longer lifespan than F4/80 (a macrophage marker)-positive macrophages. When BMP disks and control disks were implanted in RANK ligand-deficient mice, RANK-positive cells were observed in the BMP disks but not in the controls. F4/80-positive cells were distributed in both disks. Administration of FYT720, a sphingosine 1-phosphate agonist, promoted the egress of RANK-positive cells from hematopoietic tissues into bloodstream. These results suggest that lineage-determined QOPs circulate in the blood and settle in the bone. (C) 2011 American Society for Bone and Mineral Research.