Alkaline phosphatase expression during monocyte differentiation - Overlapping markers as a link between monocytic cells, dendritic cells, osteoclasts and osteoblasts

Alkaline phosphatase expression during monocyte differentiation - Overlapping markers as a link between monocytic cells, dendritic cells, osteoclasts and osteoblasts
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DOI:
10.1016/s0171-2985(00)80054-6
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发表时间:
2000-05-01
期刊:
影响因子:
2.8
通讯作者:
Peters, JH
Peters, JH
中科院分区:
医学4区
文献类型:
--
作者:
Heinemann, DEH;Siggelkow, H;Peters, JH

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体外培养的人单核细胞可分化为巨噬细胞(M Phi)、树突状细胞(DC)和破骨细胞。此外,我们还建立了一种钼来源的体外肉芽肿模型,并与体外分离的异物肉芽肿细胞进行了比较。在这些模型中,单核细胞来源的树突状细胞(MoDC)、破骨细胞、M Phi和成骨细胞之间形成了重叠的表型。在Mo培养中,固定化颗粒材料可诱发肉芽肿。AP活性(成骨细胞标记物)与胞浆抗酒石酸酸性磷酸酶(TRAP)共表达,作为破骨细胞标记物。在增殖过程中,AP(+)细胞数量减少,取而代之的是共表达破骨细胞标志物玻璃体连接素受体(VNR)和TRAP的细胞。Mo/M Phi标记物CD68与AP或VNR共表达证实细胞来源于单核细胞。用白介素4(IL-4)处理钼时,AP(+)细胞数量显著增加,并在12d内保持稳定表达。从人工内翻修获得的体外肉芽肿外植体中,主要的细胞类型是共表达CD68的AP(+)细胞。在体外培养的肉芽肿细胞中检测骨特异性碱性磷酸酶(BAP)作为成骨细胞的标志物。通过RT-PCR检测成骨细胞的高度特异性标志物骨钙素的mRNA。根据我们的结果,我们得出巨噬细胞、DC和破骨细胞之间的个体发育关系。此外,数据表明钼和成骨细胞之间存在转分化。
Human monocytes (Mo) in culture can be differentiated into macrophages (M phi), dendritic cells (DC) and osteoclasts. In addition, we have established a Mo-derived in vitro granuloma model which here was compared with ex-vivo isolated foreign body granuloma cells. In these models overlapping phenotypes developed between monocyte-derived dendritic cells (MoDC), osteoclasts, M phi, and osteoblasts. In Mo cultures granulomas were induced by immobilized particulate material. AP activity (osteoblast marker) was found to be co-expressed with cytoplasmic tartrate resistant acid phosphatase (TRAP) as a marker of osteoclasts. While proliferating, the number of AP(+) cells decreased, being replaced by cells co-expressing the osteoclast markers vitronectin receptor (VNR) and TRAP. Coexpression of the Mo/M phi marker CD68 with AP or VNR confirmed the monocytic origin of the cells. When Mo were treated with interleukin-4 (IL-4), the number of AP(+) cells markedly increased and remained stably expressed over 12 days. In explants from ex vivo granulomas obtained from endoprosthetic revisions the major cell type was the AP(+) cell co-expressing CD68. The bone-specific alkaline phosphatase (BAP) as a marker of osteoblasts was detected by FAGS analysis in the ex vivo granuloma cells. By RT-PCR the mRNA for osteocalcin, which is a highly specific marker fur osteoblasts, was detected. From our results we conclude an ontogenetic relationship between macrophages, DC and osteoclasts. Furthermore, the data suggest a transdifferentiation between Mo and osteoblasts.