title: Analysis of gene expression profiles in human periodontal ligament cells under hypoxia: the protective effect of CC chemokine ligand 2 to oxygen shortage.
abstract: Periodontal ligament (PDL) cells appear to play important functional roles in response to mechanical stress. We hypothesized that hypoxia caused by a deformation of blood vessels and the following ischaemia may play a crucial role in differential gene expression in PDL cells affected by mechanical stress. Gene induction in cultured human PDL cells by hypoxia was analyzed using cDNA array, followed by RT-PCR analysis. Eleven hypoxia-responsive genes were found differentially expressed under low-oxygen conditions in PDL cells. Among them, CCR2, CC chemokine ligand 2 (CCL2) receptor was studied in more detail since little information is available on the role of chemokines in adaptive responses of PDL cells under hypoxia. Here we investigate whether CCR2 mediates the signalling to maintain the homeostasis of PDL cells. We found that cell death of PDL cells was induced under hypoxia with down-regulation of CCL2 mRNA expression. However, the exogenous CCL2 prevented PDL cell death under oxygen shortage with the increment of cellular inhibitor of apoptosis (cIAP) mRNA expression. The present study demonstrated substantial effects of hypoxia on gene expression of CCL2 and CCR2 in PDL cells, indicating that mechanical loading accompanied with mild hypoxia allows PDL cells to elicit adaptive responses with up-regulation of CCR2.
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kitase
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yokozeki
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Izawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Kuroda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
mesh_terms: D017209:Apoptosis / Q000235:genetics; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D016923:Cell Death / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010513:Periodontal Ligament / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013314:Stress, Mechanical; D044767:Ubiquitin-Protein Ligases
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases