Padial-Molina M, Volk S L, Rios H F
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Department of Oral Surgery and Implant Dentistry, School of Dentistry, University of Granada, Granada, Spain.
J Periodontal Res. 2014 Jun;49(3):405-14. doi: 10.1111/jre.12120. Epub 2013 Aug 6.
In the chronic established periodontal lesion, the proliferation and migration potential of periodontal ligament (PDL) cells are significantly compromised. Thus, the progressive loss of tissue integrity is favored and normal healing and regeneration compromised. Periostin, a known PDL marker, modulates cell-matrix interactions, cell behavior, as well as the matrix biomechanics and PDL homeostasis.
To evaluate whether periostin restores the regenerative potential of PDL cells in terms of proliferation, migration, and activation of survival signaling pathways after being challenged by Porphyromonas gingivalis lipopolysaccharides and tumor necrosis factor alpha α.
Human PDL (hPDL) cells were cultured under different conditions: control, periostin (50 or 100 ng/mL), and fibroblast growth factor 2 (10 ng/mL) to evaluate cell proliferation (by Ki67), cell migration (by scratch assays) and PI3K/AKT/mTOR pathway activation (by western blot analyses of total AKT, phospho-AKT and PS6). A different set of cultures was challenged by adding tumor necrosis factor alpha α (10 ng/mL) and P. gingivalis lipopolysaccharides (200 ng/mL) to evaluate the effects of periostin as described above.
Periostin significantly increased cell proliferation (twofold), migration (especially at earlier time points and low dose) and activation of survival signaling pathway (higher phosphorylation of AKT and PS6). Furthermore, periostin promoted similar cellular effects even after being challenged with proinflammatory cytokines and bacterial virulence factors.
Periostin acts as an important modulator of hPDL cell-matrix dynamics. It modulates hPDL proliferation, migration and PI3K/AKT/mTOR pathway. It also helps in overcoming the altered biological phenotype that chronic exposure to periodontal pathogens and proinflammatory cytokines produce in hPDL cells.
在慢性牙周病变期,牙周膜(PDL)细胞的增殖和迁移能力显著受损。因此,组织完整性逐渐丧失,正常愈合和再生受到影响。骨膜蛋白是一种已知的牙周膜标志物,可调节细胞与基质的相互作用、细胞行为以及基质生物力学和牙周膜内环境稳定。
评估在受到牙龈卟啉单胞菌脂多糖和肿瘤坏死因子α刺激后,骨膜蛋白是否能在增殖、迁移和存活信号通路激活方面恢复牙周膜细胞的再生潜能。
将人牙周膜(hPDL)细胞在不同条件下培养:对照组、骨膜蛋白(50或100 ng/mL)组和成纤维细胞生长因子2(10 ng/mL)组,以评估细胞增殖(通过Ki67)、细胞迁移(通过划痕试验)和PI3K/AKT/mTOR通路激活(通过对总AKT、磷酸化AKT和PS6进行蛋白质印迹分析)。另一组培养物通过添加肿瘤坏死因子α(10 ng/mL)和牙龈卟啉单胞菌脂多糖(200 ng/mL)进行刺激,以评估骨膜蛋白的上述作用。
骨膜蛋白显著增加细胞增殖(两倍)、迁移(尤其是在早期时间点和低剂量时)以及存活信号通路的激活(AKT和PS6的磷酸化水平更高)。此外,即使在受到促炎细胞因子和细菌毒力因子刺激后,骨膜蛋白仍能促进类似的细胞效应。
骨膜蛋白是hPDL细胞与基质动态变化的重要调节因子。它调节hPDL细胞的增殖、迁移和PI3K/AKT/mTOR通路。它还有助于克服长期暴露于牙周病原体和促炎细胞因子在hPDL细胞中产生的生物学表型改变。