Double-edged-sword effect of IL-1β on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κB, MAPK and BMP/Smad signaling pathways.
Double-edged-sword effect of IL-1β on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κB, MAPK and BMP/Smad signaling pathways.
复制标题
IL-1β对NF-κB，MAPK和BMP/BMP/SMAD信号通路之间的串扰，对IL-1β对牙周韧带干细胞的成骨的双重词作用。
DOI：
10.1038/cddis.2016.204
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发表时间：
2016-07-14
影响因子：
9
通讯作者：
Lu EY
中科院分区：
文献类型：
--
作者：
Mao CY;Wang YG;Zhang X;Zheng XY;Tang TT;Lu EY
微环境条件可以干扰间充质干细胞（MSCs）的功能作用和分化。最近的研究表明，炎症微环境可以显着影响牙周膜干细胞（PDLSC）的成骨潜能，但确切的影响和机制仍不清楚。在这里，我们首次表明白细胞介素-1 β（IL-1β）在PDLSC的成骨中具有双重作用，其浓度范围从生理健康水平到慢性牙周炎中发现的浓度。低剂量IL-1β激活BMP/Smad信号通路促进PDLSCs成骨，高剂量IL-1β通过激活核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路抑制BMP/Smad信号通路，抑制成骨。这些结果表明NF-κB、MAPK和BMP/Smad信号之间的串扰介导IL-1β对PDLSC的这种双重作用。我们还发现，PDLSCs的成骨功能受损导致更多的炎性细胞因子和趋化因子释放，诱导巨噬细胞的趋化性，这进一步阐明了PDLSCs在牙周炎发病机制中的作用。
Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs). Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs), but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin-1β (IL-1β) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL-1β activate the BMP/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL-1β inhibit BMP/Smad signaling through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF-κB, MAPK and BMP/Smad signaling mediates this dual effect of IL-1β on PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.