Pabst Andreas Max, Krüger Maximilian, Ziebart Thomas, Jacobs Collin, Sagheb Keyvan, Walter Christian
Department of Oral and Maxillofacial Surgery (Head: Univ.-Prof. Dr. Dr. W. Wagner), University Medical Center Mainz, Augustusplatz 2, 55131 Mainz, Germany.
Department of Oral and Maxillofacial Surgery (Head: Univ.-Prof. Dr. Dr. W. Wagner), University Medical Center Mainz, Augustusplatz 2, 55131 Mainz, Germany.
J Craniomaxillofac Surg. 2015 Jun;43(5):688-95. doi: 10.1016/j.jcms.2015.03.014. Epub 2015 Mar 27.
This in vitro study analyzed the influence of geranylgeraniol (GGOH) on human oral keratinocytes (HOK) after exposure to bisphosphonates. HOK were incubated with four different bisphosphonates (clodronate, ibandronate, pamidronate, zoledronate) in two experimental set-ups: with and without GGOH. MTT and PrestoBlue assays were used to analyze HOK cell viability. HOK migration ability was examined with Boyden and Scratch assays, and Tunel and ToxiLight assays were used to detect the HOK apoptosis rate. No significant differences between the experimental set-ups, with and without GGOH, could be found for clodronate (p each >0.3). For the nitrogen-containing bisphosphonates, negative effects could be shown in the experimental set-ups without GGOH in all assays. In the GGOH experimental set-ups, the levels of HOK cell viability were significantly increased (MTT: p each ≤0.001; PrestoBlue: p each ≤0.012). The HOK migration ability was also greater (Boyden: p each <0.001; Scratch: p each ≤0.015). Regarding the apoptosis rate, reduced numbers of apoptotic HOK in the Tunel assay (p each <0.001) and decreased adenylate kinase release in the ToxiLight assay (p each ≤0.002) were observed. GGOH reversed the negative effects of bisphosphonates on HOK. These findings provide evidence that GGOH could be a promising treatment option for BP-ONJ.
这项体外研究分析了香叶基香叶醇（GGOH）对双膦酸盐暴露后人口腔角质形成细胞（HOK）的影响。在两种实验设置下，将HOK与四种不同的双膦酸盐（氯膦酸盐、伊班膦酸盐、帕米膦酸盐、唑来膦酸盐）一起孵育：添加和不添加GGOH。采用MTT和PrestoBlue检测法分析HOK细胞活力。用博伊登实验和划痕实验检测HOK迁移能力，并用Tunel和ToxiLight检测法检测HOK凋亡率。对于氯膦酸盐，添加和不添加GGOH的实验设置之间未发现显著差异（各p>0.3）。对于含氮双膦酸盐，在所有检测中，不添加GGOH的实验设置均显示出负面影响。在添加GGOH的实验设置中，HOK细胞活力水平显著提高（MTT：各p≤0.001；PrestoBlue：各p≤0.012）。HOK迁移能力也更强（博伊登实验：各p<0.001；划痕实验：各p≤0.015）。关于凋亡率，在Tunel检测中观察到凋亡HOK数量减少（各p<0.001），在ToxiLight检测中腺苷酸激酶释放减少（各p≤0.002）。GGOH逆转了双膦酸盐对HOK的负面影响。这些发现提供了证据，表明GGOH可能是治疗双膦酸盐相关颌骨坏死（BP-ONJ）的一种有前景的治疗选择。
