Diercke Katja, Zingler Sebastian, Kohl Annette, Lux Christopher J, Erber Ralf
, Heidelberg, Germany,
Clin Oral Investig. 2014 Nov;18(8):1925-39. doi: 10.1007/s00784-013-1167-0. Epub 2014 Jan 10.
Root resorptions due to a reduced repair function of cementoblasts are common side effects during orthodontic tooth movement (OTM). The mechanisms, which lead to an impaired cementoblast function, are not fully understood. Therefore, we aimed to investigate changes in the gene expression of cementoblasts during mechanical stimulus under inflammatory conditions.
Human primary cementoblasts (HPCB) were exposed to compression for 6 h or stimulation with IL-1β for 96 h and subsequent 6 h compression. Genome-wide expression analysis was performed using microarray analysis. Prominent gene expression alterations (COX2, AXUD1, FOSB, CCL2, IFI6, and PTGES) were verified by quantitative RT-PCR (qRT-PCR) in two HPCB populations. A caspase 3/7 activity assay was used to determine caspase-3 and caspase-7 activity in stressed cells.
Gene expression cluster analysis revealed apoptosis as an important process induced under both conditions. Apoptosis (pro- and anti-apoptotic) related gene expression was most relevant after pro-inflammatory stimulation and compression. qRT-PCR analysis confirmed significant up-regulation of COX2, AXUD1, and FOSB in both HPCB populations after compression, while selected genes significantly increased after pro-inflammatory stimulation and compression. Compression of cementoblasts increased caspase. The combination of pro-inflammatory stimulation and compression led to a slightly smaller increase of caspase activity.
Gene ontology analysis showed that compressed HPCB up-regulate genes that are associated with apoptosis. Combining compression with a pro-inflammatory stimulus (IL-1β) augmented the positive regulation of apoptosis-related pathways. The induction of apoptosis related gene expression (pro- and anti-apoptotic genes) in cementoblasts suggests an involvement of apoptosis in cementoblast regulation during OTM.
As apoptosis is induced in HPCB after compression and inflammation, it is conceivable that HPCB cell death might contribute to root resorptions due to a loss of repair activity of cementoblasts. Further studies should be conducted to clarify the implication of the identified genes on root resorptions in order to develop therapeutic strategies to prevent a shortening of roots.
成牙骨质细胞修复功能降低导致的牙根吸收是正畸牙齿移动（OTM）过程中常见的副作用。导致成牙骨质细胞功能受损的机制尚未完全明确。因此，我们旨在研究炎症条件下机械刺激过程中成牙骨质细胞基因表达的变化。
将人原代成牙骨质细胞（HPCB）进行6小时的压缩处理，或用白细胞介素-1β刺激96小时，随后进行6小时的压缩处理。使用微阵列分析进行全基因组表达分析。在两个HPCB群体中通过定量逆转录聚合酶链反应（qRT-PCR）验证了显著的基因表达改变（COX2、AXUD1、FOSB、CCL2、IFI6和PTGES）。使用半胱天冬酶3/7活性测定法来确定应激细胞中的半胱天冬酶-3和半胱天冬酶-7活性。
基因表达聚类分析显示凋亡是在两种条件下诱导的重要过程。促炎刺激和压缩后，凋亡（促凋亡和抗凋亡）相关基因表达最为相关。qRT-PCR分析证实，两个HPCB群体在压缩后COX2、AXUD1和FOSB均显著上调，而在促炎刺激和压缩后选定基因显著增加。成牙骨质细胞的压缩增加了半胱天冬酶活性。促炎刺激和压缩的联合作用导致半胱天冬酶活性的增加略小。
基因本体分析表明，压缩后的HPCB上调了与凋亡相关的基因。将压缩与促炎刺激（白细胞介素-1β）相结合增强了凋亡相关途径的正向调节。成牙骨质细胞中凋亡相关基因表达（促凋亡和抗凋亡基因）的诱导表明凋亡参与了OTM过程中成牙骨质细胞的调节。
由于压缩和炎症后HPCB中诱导了凋亡，可以想象HPCB细胞死亡可能由于成牙骨质细胞修复活性丧失而导致牙根吸收。应进行进一步研究以阐明所鉴定基因对牙根吸收的影响，从而制定预防牙根缩短的治疗策略。
