Development of osteoclasts from embryonic stem cells through a pathway that is c-fms but not c-kit dependent
Development of osteoclasts from embryonic stem cells through a pathway that is c-fms but not c-kit dependent
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DOI：
10.1182/blood.v90.9.3516
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发表时间：
1997-11-01
期刊：
影响因子：
20.3
通讯作者：
Hayashi, SI
中科院分区：
文献类型：
--
作者：
Yamane, T;Kunisada, T;Hayashi, SI
破骨细胞是骨吸收所必需的造血细胞，为了研究破骨细胞的来源，我们建立了一个逐步培养系统，其中基质细胞促进胚胎干细胞（ES细胞）分化为成熟的破骨细胞。该分化过程的三个阶段包括（1）造血的诱导，沿着破骨细胞前体的产生，（2）这些前体的扩增，和（3）在1 α，25-二羟维生素D-3存在下终末分化为成熟破骨细胞。虽然ES细胞向造血谱系的转变没有被c-fms的抗体阻断，但是后期依赖于通过这种跨膜受体的信号传导，如发现在第二和第三阶段中细胞的抗c-fms处理分别使产生的破骨细胞的数量减少75%和超过99%所指示的。通过另一种酪氨酸激酶型受体的信号传导的阻断，c-kit不影响破骨细胞生成的任何阶段，尽管其它造血谱系的产生减少到小于未处理的10%。当在促进破骨细胞分化的条件下直接培养少量ES细胞时，在集落的边缘而不是内部观察到抗酒石酸盐酸性磷酸酶阳性的多核细胞，这表明某些类型的细胞-细胞相互作用可能抑制成熟破骨细胞的发育。这里开发的培养系统为破骨细胞生物学提供了重要工具，（C）1997年由美国血液学会。
Osteoclasts are hematopoietic cells essential for bone resorption, To study the derivation of these interesting cells, we developed a stepwise culture system where stromal cells promote embryonic stem (ES) cells to differentiate into mature osteoclasts. Three phases to this differentiation process include (1) induction of hematopoiesis, along with the generation of osteoclast precursors, (2) expansion of these precursors, and (3) terminal differentiation into mature osteoclasts in the presence of 1 alpha, 25-dihydroxyvitamine D-3. Although the transition of ES cells to the hematopoietic lineage was not blocked by an antibody to c-fms, later phases were dependent on a signaling through this transmembrane receptor as indicated by the finding that anti-c-fms-treatment of cells in the second and third phases reduced the number of osteoclasts produced by 75% and more than 99%, respectively, Blockade of signaling through another tyrosine kinase-type receptor, c-kit did not affect any stages of osteoclastogenesis, although generation of other hemopoietic lineages was reduced to less than 10% of untreated. When small numbers of ES cells were directly cultured under conditions that promote osteoclast differentiation, tartrate-resistant acid phosphatase-positive multinucleated cells were observed at the edge but not inside of colonies, This suggests that some types of cell-cell interactions may inhibit development of mature osteoclasts. The culture system developed here provides an important tool for osteoclast biology, (C) 1997 by The American Society of Hematology.