Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Oral Dis. 2019 Nov;25(8):1972-1982. doi: 10.1111/odi.13167. Epub 2019 Oct 18.
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.
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.
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.
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.
巨噬细胞可以被完全极化，并获得特定的表型，如 M1，这被认为是牙周炎发展过程中肺泡骨破坏所必需的。然而，M1 巨噬细胞对肺泡骨破坏的影响的分子机制尚不清楚。
建立小鼠牙周炎模型，以确定 M1 巨噬细胞在发病机制中的作用。用 M1 巨噬细胞的条件培养基（M1-CM）孵育成骨前体细胞，以评估其对成骨作用的影响。用 CM 处理后的细胞进行 RNA 测序、定量 PCR、Western blot 和免疫荧光染色，以确定参与成骨作用抑制的途径。
牙周炎中 M1 巨噬细胞的浸润增加与肺泡骨破坏有关。M1-CM 明显抑制成骨细胞的生成，表现为 Runx2 和 Ocn 表达降低，以及 ALP 活性降低。有趣的是，RNA 测序表明，CM 处理的成骨前体细胞中 TLR4/AP1 信号通路被激活。TLR4 抑制减少了 AP1 的易位，并挽救了 M1-CM 减少的成骨作用。
M1 巨噬细胞通过旁分泌诱导成骨前体细胞的 TLR4/AP1 信号，抑制成骨作用，至少部分导致牙周炎中肺泡骨的破坏。
