Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration.
Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration.
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DOI：
10.1038/boneres.2015.14
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发表时间：
2015
期刊：
影响因子：
12.7
通讯作者：
McCauley LK
中科院分区：
文献类型：
--
作者：
Chang J;Koh AJ;Roca H;McCauley LK
骨髓含有异质的细胞环境，包括巨噬细胞，巨噬细胞是解决感染和炎症的关键细胞介质。巨噬细胞吞噬异物或凋亡细胞以维持体内平衡的能力是众所周知的;然而，对其在骨微环境中的功能知之甚少。在目前的研究中，我们研究了小鼠巨噬细胞和骨髓基质细胞（BMSC）的体外相互作用，重点是阿曲他克林诱导IL-6信号转导和对BMSC迁移和生长的影响。原代小鼠巨噬细胞和BMSC的阿曲他克林相互作用激活了共培养物中的IL-6信号传导，随后增强了BMSC迁移并增加了BMSC数量。从IL-6敲除小鼠收获的BMSC和巨噬细胞显示，IL-6信号传导对于增强BMSC迁移和通过阿曲他克林相互作用增加BMSC数量是必需的。BMSC是IL-6信号传导的主要贡献者，因此激活了IL-6/gp 130/STAT 3通路。同时，巨噬细胞衍生的IL-6对于共培养物中IL-6蛋白的总体产生仍然重要。总之，这些发现表明巨噬细胞作为BMSCs迁移和生长的共诱导剂的功能，这可能直接影响骨形成和转换。
The bone marrow contains a heterogeneous milieu of cells, including macrophages, which are key cellular mediators for resolving infection and inflammation. Macrophages are most well known for their ability to phagocytose foreign bodies or apoptotic cells to maintain homeostasis; however, little is known about their function in the bone microenvironment. In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells (BMSCs), with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth. The juxtacrine interaction of primary mouse macrophages and BMSCs activated IL-6 signaling in the co-cultures, which subsequently enhanced BMSC migration and increased BMSC numbers. BMSCs and macrophages harvested from IL-6 knockout mice revealed that IL-6 signaling was essential for enhancement of BMSC migration and increased BMSC numbers via juxtacrine interactions. BMSCs were the main contributor of IL-6 signaling, and hence activation of the IL-6/gp130/STAT3 pathway. Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures. Taken together, these findings show the function of macrophages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.