An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand
An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand
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DOI：
10.1182/blood.v96.13.4335.h8004335_4335_4343
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发表时间：
2000-12-15
期刊：
影响因子：
20.3
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Miyamoto, T;Arai, F;Suda, T
核因子 KB 受体激活剂 (RANK) 和 RANK 配体 (RANKL) 的鉴定为破骨细胞分化途径提供了新的见解。使用针对 c-Fms 和 RANK 的单克隆抗体分离破骨细胞前体细胞，并在 2 种不同类型的无基质细胞培养系统：半固体培养基（非贴壁系统）和液体培养基（贴壁系统）中检查贴壁对这些细胞体外分化和增殖的影响。破骨细胞前体细胞在半固体培养系统中不能有效分化为成熟的破骨细胞。三聚化的 RANKL 增强了半固体培养物中的破骨细胞分化，但未达到允许细胞粘附到塑料上时所观察到的程度。最初的前体细胞能够分化为巨噬细胞或破骨细胞，一旦将这些细胞转移到贴壁条件下，就会诱导显着的分化。即使在表现出吞噬活性后仍观察到多核细胞，这表明细胞粘附在破骨细胞前体细胞的分化中起着重要作用。整合素，尤其是识别精氨酸-甘氨酸-天冬氨酸（RGD）的整合素α（nu）和β（3），是破骨细胞定向前体细胞增殖以形成多核破骨细胞所必需的，并且细胞密度的增加影响多核细胞的形成。提出了具有两个前体发育阶段的破骨细胞分化模型：（1）第一阶段，其中前体细胞具有双能性并且能够进行不依赖贴壁的生长；（2）第二阶段，其中破骨细胞定向前体细胞的进一步增殖和分化是贴壁依赖性的。 (Blood. 2000;96: 4335-4343) (C) 2000 年，美国血液学会。
Identification of receptor activator of nuclear factor-KB (RANK) and RANK-ligand (RANKL) has provided new insights into the osteoclast differentiation pathway. Osteoclast precursor cells were isolated using monoclonal antibodies against c-Fms and RANK, and the effect of adherence on the in vitro differentiation and proliferation of these cells was examined in 2 different types of stromal-cell-free culture systems: a semisolid culture medium (a nonadherent system) and a liquid culture medium (an adherent system). Osteoclast precursor cells were not able to differentiate into mature osteoclasts efficiently in the semisolid culture system. Trimerized RANKL enhanced osteoclast differentiation in semisolid cultures, but not to the extent seen when cells were allowed to adhere to plastic. Initial precursor cells were capable of differentiating into macrophages or osteoclasts, Once these cells were transferred to adherent conditions, striking differentiation was induced. Multinuclear cells were observed even after they had displayed phagocytic activity, which suggests that cell adhesion plays an important role in the differentiation of osteoclast precursor cells. Integrins, especially the arginine-glycine-aspartic acid (RGD)-recognizing integrins alpha (nu) and beta (3), were needed for osteoclast-committed precursor cells to proliferate in order to form multinuclear osteoclasts, and the increase in cell density affected the formation of multinuclear cells. A model of osteoclast differentiation with 2 stages of precursor development is proposed: (1) a first stage, in which precursor cells are bipotential and capable of anchorage-independent growth, and (2) a second stage, in which the further proliferation and differentiation of osteoclast-committed precursor cells is anchorage-dependent. (Blood. 2000;96: 4335-4343) (C) 2000 by The American Society of Hematology.