Compression of human primary cementoblasts leads to apoptosis: A possible cause of dental root resorption?

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.