Department of Operative Dentistry and Endodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, Zhejiang, China.
Cytokine. 2022 Oct;158:155983. doi: 10.1016/j.cyto.2022.155983. Epub 2022 Aug 2.
The key to prevent pulp necrosis in the early stage of pulpitis is to promote tissue repair, which begins with cell migration. Stromal cell-derived factor 1α (SDF-1α) has been proven to promote cell migration. Related research has so far concentrated on the biological effects of SDF-1α while its expression in pulpitis is still unclear. We investigated the effect of inflammation on SDF-1α in dental pulp and the underlying regulatory mechanisms. First, rat pulpitis models were established by exposing pulp. SDF-1α was decreased on the 3rd day but increased on the 7th day. Next, lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) was applied to dental pulp cells (DPCs). Within 24 h, SDF-1α decreased, but after 48 h, it steadily increased. Similarly, SDF-1α expression in human chronic pulpitis tissues was also increased. To investigate the effect of altered SDF-1α on DPC migration, cell supernatants collected following Pg.LPS treatment were utilized to stimulate DPCs, and the number of migrated cells was correlated with changes in SDF-1α secretion. Finally, we explored the regulatory mechanisms of SDF-1α down-regulation in the early phase of pulpitis. Within 24 h, JNK/c-Jun pathway was activated in DPC inflammation. When JNK pathway was suppressed, SDF-1α rose. Furthermore, tumor necrosis factor receptor 2 (TNFR2) and apoptosis signal-regulated kinase-interacting protein 1 (AIP1) were up-regulated. Knockdown of them abolished Pg.LPS-induced activation of JNK and c-Jun(Ser63) and significantly enhanced SDF-1α. Our findings indicated that in the early phase of pulpitis, inflammation suppressed SDF-1α by up-regulating TNFR2 and AIP1, which activated JNK/c-Jun(Ser63) pathway.
预防牙髓炎早期牙髓坏死的关键在于促进组织修复,这始于细胞迁移。基质细胞衍生因子 1α(SDF-1α)已被证明可促进细胞迁移。相关研究迄今为止集中在 SDF-1α 的生物学效应上,而其在牙髓炎中的表达仍不清楚。我们研究了炎症对牙髓中 SDF-1α 的影响及其潜在的调节机制。首先,通过暴露牙髓建立大鼠牙髓炎模型。第 3 天 SDF-1α 减少,第 7 天增加。接下来,将牙龈卟啉单胞菌(Pg.LPS)的脂多糖应用于牙髓细胞(DPC)。24 小时内,SDF-1α 减少,但 48 小时后,其稳定增加。同样,人慢性牙髓炎组织中 SDF-1α 的表达也增加。为了研究改变的 SDF-1α 对 DPC 迁移的影响,使用经 Pg.LPS 处理后的细胞上清液刺激 DPC,迁移细胞的数量与 SDF-1α 分泌的变化相关。最后,我们探讨了牙髓炎早期 SDF-1α 下调的调节机制。24 小时内,DPC 炎症中激活了 JNK/c-Jun 通路。当 JNK 通路被抑制时,SDF-1α 上升。此外,肿瘤坏死因子受体 2(TNFR2)和凋亡信号调节激酶相互作用蛋白 1(AIP1)上调。它们的敲低消除了 Pg.LPS 诱导的 JNK 和 c-Jun(Ser63)的激活,并显著增强了 SDF-1α。我们的研究结果表明,在牙髓炎的早期阶段,炎症通过上调 TNFR2 和 AIP1 抑制 SDF-1α,从而激活 JNK/c-Jun(Ser63)通路。