HMGB1-induced inflammatory response promotes bone healing in murine tooth extraction socket
HMGB1-induced inflammatory response promotes bone healing in murine tooth extraction socket
复制标题
DOI：
10.1002/jcb.26710
复制
发表时间：
2018-07-01
影响因子：
4
通讯作者：
Takashiba, Shogo
中科院分区：
文献类型：
--
作者：
Aoyagi, Hiroaki;Yamashiro, Keisuke;Takashiba, Shogo
高迁移率族蛋白 1 (HMGB1) 是一种非组蛋白 DNA 结合蛋白，响应炎症刺激而分泌到细胞外环境中。分泌的 HMGB1 被认为可以介导各种炎症性疾病。然而，HMGB1是否参与拔牙槽、含有牙龈上皮的组织和暴露于口腔细菌的牙槽骨的愈合过程仍不清楚。在本研究中，我们构建了给予抗HMGB1中和抗体的小鼠拔牙模型，并通过髓过氧化物酶（MPO）活性的分子成像、组织学分析和定量RT-PCR观察拔牙槽中的炎症反应和骨愈合过程。施用抗HMGB1抗体可抑制牙龈上皮细胞和炎症细胞中HMGB1从细胞核易位至细胞质。抗HMGB1抗体处理样本中拔牙槽周围的MPO活性显着降低，并且CD31和CD68阳性细胞的数量显着低于对照样本。抗HMGB1抗体处理样品中TRAP阳性细胞、骨钙素阳性细胞和肿瘤骨面积显着低于对照样品。与对照样品相比，抗HMGB1抗体处理样品中IL-1和VEGF-A的表达水平也降低。拔牙后分泌的 HMGB1 诱导初始急性炎症和炎症细胞募集。 HMGB1 与破骨细胞和成骨细胞激活引起的血管生成和骨重塑相关，并促进拔牙槽中的骨愈合。
High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 has been suggested to mediate various inflammatory diseases. However, it is still unknown whether HMGB1 is involved in a healing process in the tooth extraction socket, the tissue containing gingival epithelium, and alveolar bone that is exposed to oral bacteria. In this study, we constructed a murine tooth extraction model with anti-HMGB1 neutralization antibody administration and observed the inflammatory response and bone healing process in tooth extraction sockets by molecular imaging of myeloperoxidase (MPO) activity, histological analysis, and quantitative RT-PCR. The translocation of HMGB1 from the nucleus to the cytoplasm in gingival epithelial cells and inflammatory cells was inhibited by anti-HMGB1 antibody administration. The MPO activity around the tooth extraction socket was significantly reduced, and the numbers of CD31- and CD68-positive cells were significantly lower in the anti-HMGB1 antibody treatment samples than in the control samples. The TRAP-positive cells, osteocalcin positive cells, and the neoplastic bone area were significantly lower in anti-HMGB1 antibody treatment samples than in control samples. The expression levels of IL-1 and VEGF-A were also decreased in anti-HMGB1 antibody treatment samples compared to that in control samples. Secreted HMGB1 induced initial acute inflammation and inflammatory cells recruitment after tooth extraction. HMGB1 was associated with angiogenesis and bone remodeling by osteoclast and osteoblast activation and promoted bone healing in the tooth extraction socket.