PMID- 30587688 OWN - NLM STAT- MEDLINE DCOM- 20190514 LR - 20190514 IS - 1880-4926 (Electronic) IS - 1343-4934 (Linking) VI - 60 IP - 4 DP - 2018 TI - Effect of hypoxia on the expression of CCAAT/enhancer-binding protein beta and receptor activator of nuclear factor kappa-B ligand in periodontal ligament cells. PG - 544-551 LID - 10.2334/josnusd.17-0436 [doi] AB - Hypoxia after traumatic injuries to a tooth is one of the causes of subsequent root resorption. Inflammatory cytokines produced under hypoxic conditions are associated with root resorption, but the mechanism has not been fully understood. In this study, the role of hypoxia-inducible factor-1 (HIF-1) signaling in the regulation of CCAAT (cytosine-cytosine-adenosine-adenosine-thymidine)/enhancer-binding protein-beta (C/EBPbeta) and the receptor activator of nuclear factor kappa-B ligand (RANKL) expressions in immortalized human periodontal ligament (PDL) cells was investigated. PDL cells cultured under a hypoxic condition showed an increase in the expression of C/EBPbeta and RANKL messenger RNAs (mRNAs), whereas the expression of osteoprotegerin and HIF-1alpha mRNAs was unaffected. Hypoxia had no effects on the secretion of interleukin (IL)-1beta, IL-6, IL-8, IL-17A, tumor necrosis factor-alpha, macrophage migration inhibitory factor, monocyte chemoattractant protein-1, and macrophage colony-stimulating factor in the culture media. Treatment of the cells with dimethyloxaloylglycine, a competitive HIF prolyl hydroxylase inhibitor, significantly increased the expression of C/EBPbeta and RANKL mRNAs. This suggested that the hypoxia-induced elevation of C/EBPbeta and RANKL mRNAs was dependent on the HIF-1 activity. PDL cells transfected with a specific small interfering RNA designed to target the C/EBPbeta gene showed a significant suppression of the RANKL mRNA. These findings indicated that C/EBPbeta may play an important role in tooth root resorption via RANKL activation in hypoxia-exposed PDL cells. FAU - Ito, Hisanori AU - Ito H AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Kifune, Takashi AU - Kifune T AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Ishiyama, Misa AU - Ishiyama M AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Iwasa, Satoko AU - Iwasa S AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Takei, Hiroki AU - Takei H AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. FAU - Hasegawa, Tomokazu AU - Hasegawa T AD - Department of Pediatric Dentistry, Tokushima University Hospital. FAU - Asano, Masatake AU - Asano M AD - Department of Pathology, Nihon University School of Dentistry. FAU - Shirakawa, Tetsuo AU - Shirakawa T AD - Department of Pediatric Dentistry, Nihon University School of Dentistry. AD - Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry. LA - eng PT - Journal Article PL - Japan TA - J Oral Sci JT - Journal of oral science JID - 9808942 RN - 0 (Amino Acids, Dicarboxylic) RN - 0 (CCAAT-Enhancer-Binding Protein-beta) RN - 0 (Cytokines) RN - 0 (RANK Ligand) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - VVW38EB8YS (oxalylglycine) SB - IM MH - Amino Acids, Dicarboxylic/pharmacology MH - Blotting, Western MH - CCAAT-Enhancer-Binding Protein-beta/*metabolism MH - Cells, Cultured MH - Cytokines/metabolism MH - Fluorescent Antibody Technique MH - Humans MH - *Hypoxia MH - Periodontal Ligament/*cytology MH - RANK Ligand/*metabolism MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Transfection OTO - NOTNLM OT - C/EBPbeta OT - HIF-1 OT - RANKL OT - hypoxia OT - periodontal ligament cells EDAT- 2018/12/28 06:00 MHDA- 2019/05/15 06:00 CRDT- 2018/12/28 06:00 PHST- 2018/12/28 06:00 [entrez] PHST- 2018/12/28 06:00 [pubmed] PHST- 2019/05/15 06:00 [medline] AID - 10.2334/josnusd.17-0436 [doi] PST - ppublish SO - J Oral Sci. 2018;60(4):544-551. doi: 10.2334/josnusd.17-0436.