M1 macrophages regulate TLR4/AP1 via paracrine to promote alveolar bone destruction in periodontitis
M1 macrophages regulate TLR4/AP1 via paracrine to promote alveolar bone destruction in periodontitis
复制标题
M1巨噬细胞通过旁分泌调节TLR4/AP1促进牙周炎牙槽骨破坏
DOI：
10.1111/odi.13167
复制
发表时间：
2019-10-18
期刊：
影响因子：
3.8
通讯作者：
Xu, Yan
中科院分区：
文献类型：
--
作者：
Zhu, Li-Fang;Li, Lu;Xu, Yan
目的巨噬细胞可以完全极化并获得像M1这样的特定表型，这被认为对于牙周炎发展过程中牙槽骨的破坏至关重要。然而，M1巨噬细胞对牙槽骨破坏影响的分子机制仍不清楚。方法建立小鼠牙周炎模型，探讨M1型巨噬细胞参与牙周炎发病过程。将 M1 巨噬细胞 (M1-CM) 的条件培养基与前成骨细胞一起孵育，以评估其对成骨细胞生成的影响。用 CM 处理后的细胞用于 RNA 测序、定量 PCR、蛋白质印迹和免疫荧光染色，以找出参与抑制成骨细胞生成的途径。结果 M1 巨噬细胞浸润增加与牙周炎中牙槽骨破坏相关。 M1-CM 显着抑制成骨细胞的生成，Runx2 和 Ocn 表达降低以及 ALP 活性降低证明了这一点。有趣的是，RNA 测序表明 CM 处理的前成骨细胞中 TLR4/AP1 信号通路被激活。 TLR4 的抑制减少了 AP1 的易位，并挽救了 M1-CM 减少的成骨细胞生成。结论 M1型巨噬细胞诱导前成骨细胞的TLR4/AP1信号传导，通过旁分泌抑制成骨细胞生成，至少部分导致牙周炎中牙槽骨的破坏。
Objective Macrophages could be fully polarized and acquire specific phenotype like M1, which considered to be essential for the alveolar bone destruction during the development of periodontitis. However, the molecular mechanisms underlying the effects of M1 macrophages on the alveolar bone destruction are still not clear yet. Methods Mouse periodontitis model was established to determine the involvement of M1 macrophages in the pathogenic process. Condition medium of the M1 macrophages (M1-CM) was incubated with pre-osteoblasts to evaluate its effects on the osteoblastogenesis. Cells after treatment with CM were used for RNA-sequencing, quantitative PCR, Western blotting, and immunofluorescence staining to figure out pathways involved in the inhibition of osteoblastogenesis. Results Increased infiltration of M1 macrophages was associated with alveolar bone destruction in periodontitis. M1-CM markedly suppressed the generation of osteoblasts as evidenced by decreased expressions of Runx2 and Ocn, as well as reduced activity of ALP. Interestingly, RNA-sequencing indicated the activation of TLR4/AP1 signaling pathway in pre-osteoblasts treated with CM. Inhibition of TLR4 reduced the translocation of AP1 and rescued the osteoblastogenesis reduced by M1-CM. Conclusion M1 macrophages induce TLR4/AP1 signaling of pre-osteoblasts to inhibit the osteoblastogenesis via paracrine, at least partially contributing to alveolar bone destruction in periodontitis.