The relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate.
The relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate.
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DOI：
10.4049/jimmunol.0902808
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发表时间：
2010-07-15
期刊：
影响因子：
--
通讯作者：
Purdue PE
中科院分区：
文献类型：
--
作者：
James DE;Nestor BJ;Sculco TP;Ivashkiv LB;Ross FP;Goldring SR;Purdue PE
在肉芽肿性炎症反应中，髓系细胞可分化为活化的吞噬巨噬细胞、创面愈合巨噬细胞、异物巨细胞和骨吸收破骨细胞。尽管人们意识到各种刺激，包括细胞因子、细胞-基质相互作用和对外来物质的挑战都可以影响髓系细胞的命运，但这些信号在这个过程中是如何整合的还知之甚少。在这项研究中，我们研究了核因子-κB受体激活剂(RANKL)诱导的破骨细胞生成和颗粒吞噬诱导的单核细胞激活之间的相互作用。了解相互关联的信号对疾病特别重要，如假体周围骨溶解，在这种疾病中，肉芽肿炎症是由靠近骨的颗粒吞噬引起的，并导致炎症性骨丢失。利用基于细胞的破骨细胞生成和吞噬实验，结合破骨细胞生成的关键调控因子的表达分析，我们在本研究中表明，疾病相关颗粒的吞噬作用抑制了RANKL介导的人单核细胞的破骨细胞生成。从机制上讲，吞噬作用通过下调RANK和c-FMS来调节这种效应，RANK和c-FMS是基本的破骨细胞因子RANKL和M-CSF的受体。单核细胞RANKL预处理产生的破骨前细胞抵抗等级下调，并致力于破骨细胞的形成，即使它们保持吞噬活性。因此，暴露于可吞噬颗粒和破骨细胞因子的相对时间对于决定髓系细胞的命运至关重要。
During granulomatous inflammatory reactions, myeloid cells can differentiate into activated phagocytic macrophages, wound-healing macrophages, foreign body giant cells, and bone-resorbing osteoclasts. Although it is appreciated that a variety of stimuli, including cytokines, cell–matrix interactions, and challenge with foreign materials can influence myeloid cell fate, little is known of how these signals integrate during this process. In this study, we have investigated the cross talk between receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and particle phagocytosis-induced activation of human monocytes. Understanding interconnected signals is of particular importance to disorders, such as periprosthetic osteolysis, in which granulomatous inflammation is initiated by particle phagocytosis in proximity to bone and leads to inflammatory bone loss. Using cell-based osteoclastogenesis and phagocytosis assays together with expression analysis of key regulators of osteoclastogenesis, we show in this study that phagocytosis of disease-relevant particles inhibits RANKL-mediated osteoclastogenesis of human monocytes. Mechanistically, phagocytosis mediates this effect by downregulation of RANK and c-Fms, the receptors for the essential osteoclastogenic cytokines RANKL and M-CSF. RANKL pretreatment of monocytes generates preosteoclasts that are resistant to RANK downregulation and committed to osteoclast formation, even though they retain phagocytic activity. Thus, the relative timing of exposure to phagocytosable particulates and to osteoclastogenic cytokines is critically important in the determination of myeloid cell fate.
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影响因子：
64.8
作者：
Takayanagi, H;Ogasawara, K;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
6.2
作者：
Zou, W;Bar-Shavit, Z
通讯作者：
Bar-Shavit, Z
影响因子：
4.4
作者：
Ha, Hyunil;Lee, Jong-Ho;Lee, Zang Hee
通讯作者：
Lee, Zang Hee
DOI：
10.1196/annals.1346.014
发表时间：
2006-01-01
期刊：
SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING
影响因子：
--
作者：
Ross, F. Patrick
通讯作者：
Ross, F. Patrick
影响因子：
4.4
作者：
Takami, M;Kim, N;Choi, Y
通讯作者：
Choi, Y