IL-1β Inhibits Human Osteoblast Migration
IL-1β Inhibits Human Osteoblast Migration
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DOI：
10.2119/molmed.2012.00058
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发表时间：
2013-01-01
影响因子：
5.7
通讯作者：
Brenner, Rolf E.
中科院分区：
文献类型：
--
作者：
Hengartner, Nina-Emily;Fiedler, Joerg;Brenner, Rolf E.
骨骼具有很强的自我更新和修复能力。然而，已知白介素1 β (IL-1 β)的局部分泌延长与严重的骨质流失和骨折愈合延迟有关。由于IL-1 β诱导骨吸收可能不能充分解释这些病理过程，我们在体外研究了IL-1 β是否以及如何影响多能间充质基质细胞（MSC）或成骨细胞的迁移。我们发现，均匀暴露于IL-1 β显著减少了成骨细胞向趋化因子血小板衍生生长因子(PDGF)-BB和胰岛素样生长因子1 （IGF-1）的非定向和定点迁移。暴露于浓度梯度的IL-1 β诱导更强的迁移抑制，完全消除成骨细胞对PDGF-BB、IGF-1、血管内皮生长因子a （VEGF-A）和补体因子C5a的迁移反应。IL-1 β诱导的细胞外信号调节激酶1和2 （ERK1/2）和c-Jun n末端激酶（JNK）的激活和抑制这些信号通路表明IL-1 β参与了成骨细胞迁移的作用。相反，MSC的基础迁移及其向PDGF-BB的迁移活性不受IL-1 β的影响。这些结果表明，IL-1 β的存在导致成骨细胞募集受损，这可能影响骨折愈合的早期阶段，并可能与炎症性骨病中的骨重塑具有病理相关性。
Bone has a high capacity for self-renewal and repair. Prolonged local secretion of interleukin 1 beta (IL-1 beta), however, is known to be associated with severe bone loss and delayed fracture healing. Since induction of bone resorption by IL-1 beta may not sufficiently explain these pathologic processes, we investigated, in vitro, if and how IL-1 beta affects migration of multipotent mesenchymal stromal cells (MSC) or osteoblasts. We found that homogenous exposure to IL-1 beta significantly diminished both nondirectional migration and site-directed migration toward the chemotactic factors platelet-derived growth factor (PDGF)-BB and insulinlike growth factor 1 (IGF-1) in osteoblasts. Exposure to a concentration gradient of IL-1 beta induced an even stronger inhibition of migration and completely abolished the migratory response of osteoblasts toward PDGF-BB, IGF-1, vascular endothelial growth factor A (VEGF-A) and the complement factor C5a. IL-1 beta induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases (JNK) activation and inhibition of these signaling pathways suggested an involvement in the IL-1 beta effects on osteoblast migration. In contrast, basal migration of MSC and their migratory activity toward PDGF-BB was found to be unaffected by IL-1 beta. These results indicate that the presence of IL-1 beta leads to impaired recruitment of osteoblasts which might influence early stages of fracture healing and could have pathological relevance for bone remodeling in inflammatory bone disease.