Diercke Katja, Kohl Annett, Lux Christopher J, Erber Ralf
Department of Orthodontics, University of Heidelberg Medical School, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany,
J Orofac Orthop. 2014 Nov;75(6):430-45. doi: 10.1007/s00056-014-0237-5. Epub 2014 Oct 26.
One of the most common side effects of orthodontic treatment is root resorption on the pressure side of tooth movement. This is usually repaired by cementoblasts, but 1-5 % of patients eventually experiences a marked reduction in root length because no repair has occurred. The reason why cementoblasts should lose their repair function in such cases is not well understood. There is evidence from genome-wide expression analysis (Illumina HumanHT-12 v4 Expression BeadChip Kit; > 30,000 genes) that apoptotic processes are upregulated after the compression of cementoblasts, which is particularly true of the pro-apoptotic gene AXUD1.
Human primary cementoblasts (HPCBs) from two individuals were subjected to compressive loading at 30 g/cm(2) for 1/6/10 h. The cells were then evaluated for apoptosis by flow cytometry, for mRNA expression of putative genes (AXUD1, AXIN1, AXIN2) by quantitative PCR, and for involvement of c-Jun-N-terminal kinases (JNKs) in the regulation of AXUD1 via western blotting. In addition, platelet-derived growth factor receptor-β (PDGFRβ) was selectively inhibited by SU16f to analyze the effect of PDGFRβ-dependent signal transduction on AXUD1 and AXIN1 expression.
The percentage of apoptotic HPCBs rose after only 6 h of compressive loading, and 18-20 % of cells were apoptotic after 10 h. Microarray data revealed significant upregulation of the pro-apoptotic gene AXUD1 after 6 h and quantitative PCR significant AXUD1 upregulation after 6 and 10 h of compression. AXIN1 and AXIN2 expression in HPCBs was significantly increased after compressive loading. Our tests also revealed that PDGFRβ signaling inhibition by SU16f augmented the expression of AXIN1 and AXUD1 in HPCBs under compression.
Increased apoptosis of compressed HPCBs might help explain why cementoblasts, rather than invariably repairing all cases of root resorption, sometimes allow the original root length to shorten. The pathway hypothesized to lead to cementoblast apoptosis involves PDGF signaling, with this signal transduction's inhibition augmenting the expression of pro-apoptotic genes. Thus activating PDGF signaling may modify the signaling pathway for the apoptosis of cementoblasts, which would reveal a protective role of PDGF for these cells. Further studies are needed to develop strategies of treatment capable of minimizing root resorption.
正畸治疗最常见的副作用之一是牙齿移动压力侧的牙根吸收。这通常由成牙骨质细胞修复，但1%至5%的患者最终会出现牙根长度明显缩短的情况，因为没有发生修复。在这种情况下，成牙骨质细胞为何会失去其修复功能尚不清楚。全基因组表达分析（Illumina HumanHT - 12 v4表达微珠芯片试剂盒；超过30000个基因）的证据表明，成牙骨质细胞受压后凋亡过程上调，促凋亡基因AXUD1尤其如此。
从两名个体获取的人原代成牙骨质细胞（HPCBs）在30 g/cm²的压力下加载1/6/10小时。然后通过流式细胞术评估细胞凋亡情况，通过定量PCR评估假定基因（AXUD1、AXIN1、AXIN2）的mRNA表达，并通过蛋白质印迹法评估c - Jun氨基末端激酶（JNKs）在AXUD1调控中的作用。此外，用SU16f选择性抑制血小板衍生生长因子受体-β（PDGFRβ），以分析PDGFRβ依赖性信号转导对AXUD1和AXIN1表达的影响。
仅在压缩加载6小时后，凋亡的HPCBs百分比就上升，10小时后18%至20%的细胞发生凋亡。微阵列数据显示，促凋亡基因AXUD1在6小时后显著上调，定量PCR显示在压缩6小时和10小时后AXUD1显著上调。压缩加载后，HPCBs中AXIN1和AXIN2的表达显著增加。我们的测试还表明，SU16f对PDGFRβ信号的抑制增强了压缩状态下HPCBs中AXIN1和AXUD1的表达。
受压HPCBs凋亡增加可能有助于解释为什么成牙骨质细胞有时会使原始牙根长度缩短，而不是总是修复所有牙根吸收的情况。假定导致成牙骨质细胞凋亡的途径涉及血小板衍生生长因子（PDGF）信号传导，该信号转导的抑制会增加促凋亡基因的表达。因此，激活PDGF信号可能会改变成牙骨质细胞凋亡的信号通路，这将揭示PDGF对这些细胞的保护作用。需要进一步研究以制定能够使牙根吸收最小化的治疗策略。
