Relative roles of osteoclast colony-stimulating factor and macrophage colony-stimulating factor in the course of osteoclast development.

Relative roles of osteoclast colony-stimulating factor and macrophage colony-stimulating factor in the course of osteoclast development.
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DOI:
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发表时间:
1994
影响因子:
2.6
通讯作者:
T. Lee;K. Fevold;Y. Muguruma;J. Lottsfeldt;M. Lee
T. Lee;K. Fevold;Y. Muguruma;J. Lottsfeldt;M. Lee
中科院分区:
医学4区
文献类型:
--
作者:
T. Lee;K. Fevold;Y. Muguruma;J. Lottsfeldt;M. Lee

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尽管最近的研究表明,骨质疏松(OP/OP)小鼠缺乏巨噬细胞集落刺激因子(M-CSF或CSF-1),但M-CSF在未成熟破骨细胞发育中的确切作用尚不清楚。利用新近发现的破骨细胞特异性集落刺激因子(O-CSF)和体外长期骨髓培养系统,我们研究了OP/OP和对照骨髓基质细胞支持从接种的正常干细胞产生O-CSF应答的克隆性破骨细胞前体细胞(集落形成单位-破骨细胞[CFU-O])的能力。值得注意的是,在14周的实验期间,OP/OP基质细胞培养产生的非贴壁细胞是对照培养的5倍;其中平均37%的细胞是不存活的,而对照培养的细胞是8%。OP/OP培养的CFU-O数量明显高于对照培养;OP/OP和对照培养的CFU-O的增殖速度相似。从OP/OP瓶中收集的细胞与1,25(OH)2D3共同培养时,发现有较多的降钙素受体阳性细胞。这些研究清楚地表明OP/OP骨髓基质细胞可以支持从接种的干细胞中分化和增殖的破骨细胞前体细胞,并首次提供了M-CSF对于破骨细胞发育的早期阶段不是必需的实验证据。我们推测,虽然O-CSF支持破骨细胞前体细胞的增殖,但M-CSF在前体细胞的后期发育和成熟以及防止细胞死亡方面发挥了作用。
Although recent studies have shown that osteopetrotic (op/op) mice lack macrophage colony-stimulating factor (M-CSF or CSF-1), the precise role of M-CSF in the development of immature osteoclasts remains unknown. Using a recently discovered osteoclast-specific colony-stimulating factor (O-CSF) and in vitro long-term bone marrow culture systems, we investigated the ability of op/op and control marrow stromal cells to support the production of O-CSF-responsive clonogenic osteoclast progenitors (colony-forming unit-osteoclast [CFU-O]) from inoculated normal stem cells. Remarkably, op/op stromal cell cultures produced five times as many nonadherent cells as control cultures throughout the experimental period of 14 weeks; an average of 37% of these cells were nonviable compared with 8% in control cultures. Significantly higher numbers of CFU-O were found in op/op cultures than in control cultures; the CFU-O in op/op and control cultures were proliferating at a similar rate. Higher numbers of calcitonin receptor-bearing cells were found when harvested cells from op/op flasks were cultured with 1,25(OH)2D3. These studies clearly show that op/op marrow stromal cells can support the differentiation and proliferation of osteoclast progenitors from inoculated stem cells and provide the first experimental evidence that M-CSF is not essential for the early stages of osteoclast development. We hypothesize that while O-CSF supports proliferation of osteoclast progenitors, M-CSF plays a role in the later development and maturation of the progenitor as well as in the prevention of cell death.