title: Inhibition of AXUD1 attenuates compression-dependent apoptosis of cementoblasts.
abstract: OBJECTIVE
  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.
  
  
  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/cm2for 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. katja.diercke@med.uni-heidelberg.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Korb
authors.affiliation: Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Eleni
authors.initials: E
authors.lastname: Katsikogianni
authors.affiliation: Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zingler
authors.affiliation: Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Edith
authors.initials: E
authors.lastname: Daum
authors.affiliation: Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lux
authors.affiliation: Bioassay GmbH, Im Neuenheimer Feld 515, 69120, Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hohenstein
authors.affiliation: Department of Orthodontics, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Erber
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D002478:Cells, Cultured; D003739:Dental Cementum / Q000166:cytology* / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012391:Root Resorption / Q000503:physiopathology; D013314:Stress, Mechanical; D014087:Tooth Movement Techniques
chemical_list: D051017:Apoptosis Regulatory Proteins; C434543:CSRNP1 protein, human; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Mechanical stress; Orthodontics; Periodontal ligament; Programmed cell death; Root resorption; Tooth movement