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Inhibition of AXUD1 attenuates compression-dependent apoptosis of cementoblasts

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Abstract

Objectives

Root resorptions are common undesirable side effects of orthodontic treatment. In most patients, these defects are repaired by cementoblasts. However, in 1–5 % of patients, the repair fails. The repair mechanism is not well understood. Apoptosis of cementoblasts might contribute to an impaired repair of root resorptions induced by orthodontic forces.

Materials and methods

To gain insight into putative molecular pathways leading to compression-induced apoptosis of human primary cementoblasts (HPCBs), three independent cell populations were subjected to compressive loading at 5, 20, and 30 g/cm2 for 1, 6, and 10 h. The mRNA expression of AXUD1, a novel pro-apoptotic gene, was monitored by quantitative reverse transcription PCR (qRT-PCR). To identify a possible function in compression-dependent apoptosis, AXUD1 was silenced in cementoblasts using an siRNA approach. Apoptosis of cementoblasts was measured by annexin V staining and flow cytometry. The phosphorylation of c-Jun-N-terminal kinases (JNKs) was investigated by Western blotting.

Results

AXUD1 was significantly induced in a time- and force-dependent manner. The rate of apoptotic HPCBs increased by 20–40 % after 10 h of compression (30 g/cm2). Phosphorylation of JNKs was detected after 10 h at 30 g/cm2. SiRNA-mediated knockdown of AXUD1 led to decreased phosphorylation of JNKs and reduced apoptosis rates in compressed HPCBs.

Conclusions

Compression-induced apoptosis of HPCBs is mediated by AXUD1 via a JNK-dependent pathway.

Clinical relevance

AXUD1-dependent apoptosis of human cementoblasts might contribute to an impaired repair of root resorptions during orthodontic tooth movement. Further studies are needed to develop treatment strategies aiming to minimize root resorption during orthodontic tooth movement.

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Authors and Affiliations

  1. Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Katja Korb, Eleni Katsikogianni, Sebastian Zingler, Edith Daum, Christopher J. Lux & Ralf Erber

  2. Bioassay GmbH, Im Neuenheimer Feld 515, 69120, Heidelberg, Germany

    Axel Hohenstein

Authors
  1. Katja Korb
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  2. Eleni Katsikogianni
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  3. Sebastian Zingler
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  4. Edith Daum
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  5. Christopher J. Lux
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  6. Axel Hohenstein
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  7. Ralf Erber
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Correspondence to Katja Korb.

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The authors declare that they have no competing interests.

Funding

The study was supported by the University of Heidelberg, Germany.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Korb, K., Katsikogianni, E., Zingler, S. et al. Inhibition of AXUD1 attenuates compression-dependent apoptosis of cementoblasts. Clin Oral Invest 20, 2333–2341 (2016). https://doi.org/10.1007/s00784-016-1740-4

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  • DOI: https://doi.org/10.1007/s00784-016-1740-4

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