Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors.
Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors.
复制标题
DOI：
10.1084/jem.190.12.1741
复制
发表时间：
1999-12-20
期刊：
影响因子：
--
通讯作者：
Suda T
中科院分区：
文献类型：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
破骨细胞是来源于造血干细胞的终末分化细胞。然而，它们的前体细胞如何从巨噬细胞谱系分化尚不清楚。我们已经确定了破骨细胞生成的早期和晚期阶段，其中前体细胞依次表达c-Fms和核因子κB受体激活剂（RANK），并证明了巨噬细胞集落刺激因子（M-CSF）刺激了早期前体细胞（c-Fms+RANK−）中的RANK表达。尽管M-CSF和RANKL（配体）诱导晚期前体细胞（c-Fms+RANK+）定型为破骨细胞，但即使是晚期前体细胞也有分化为不含RANKL的巨噬细胞的潜力。用M-CSF预处理前体并延迟加入RANKL表明RANK表达的时间和随后RANKL的结合对于破骨细胞生成至关重要。因此，RANK-RANKL系统决定巨噬细胞分化默认途径中双能前体的破骨细胞分化。
Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor κB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms+RANK−) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms+RANK+) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK–RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.