著者

Manami Hoshi Misa Ishiyama Takashi Wada Kenchi Hase Masayuki Itoh Takashi Kikuiri Tetsuo Shirakawa

出版者

Nihon University School of Dentistry

雑誌

Journal of Oral Science (ISSN:13434934)

巻号頁・発行日

vol.65, no.2, pp.96-101, 2023 (Released:2023-03-30)

参考文献数

24

被引用文献数

1

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Purpose: Methyl-CpG binding protein 2 (MeCP2)-deficient (Mecp2−/y) mice exhibit apneas that resemble respiratory abnormalities observed in Rett syndrome (RTT) patients. The present study aimed to clarify whether Mecp2−/y mice show diurnal variations in apnea as seen in RTT and how the MeCP2 deficiency affects monoaminergic systems that control breathing.Methods: In 7-week-old Mecp2−/y mice, 24 h variation of apnea and effects of milnacipran, a serotonin/noradrenaline reuptake inhibitor, on the apnea were evaluated. The number of vesicular monoamine transporter 2 (VMAT2)-immunoreactive puncta in the caudal medulla was counted. Further, the effects of valproate (VPA) on the expression of tyrosine hydroxylase (TH) mRNA in the ventrolateral medulla of mice were assessed by RT-qPCR.Results: Apnea occurred more frequently during the light phase under a 12:12 h light/dark environment in Mecp2−/y mice and milnacipran reduced apnea during the light phase but not during the dark phase. The number of VMAT2-immunoreactive puncta was reduced in Mecp2−/y mice. VPA treatment significantly increased TH mRNA expression in Mecp2−/y mice.Conclusion: Alteration of monoaminergic systems in the caudal medulla of Mecp2−/y mice is potentially relevant to the light-sensitive diurnal increase of apnea, and an improvement in monoaminergic neurotransmission can ameliorate the diurnal increase of apnea in Mecp2−/y mice.

著者

Hisanori Ito Takashi Kifune Misa Ishiyama Satoko Iwasa Hiroki Takei Tomokazu Hasegawa Masatake Asano Tetsuo Shirakawa

出版者

Nihon University School of Dentistry

雑誌

Journal of Oral Science (ISSN:13434934)

巻号頁・発行日

vol.60, no.4, pp.544-551, 2018 (Released:2018-12-27)

参考文献数

30

被引用文献数

5

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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-β (C/EBPβ) 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/EBPβ and RANKL messenger RNAs (mRNAs), whereas the expression of osteoprotegerin and HIF-1α mRNAs was unaffected. Hypoxia had no effects on the secretion of interleukin (IL)-1β, 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/EBPβ and RANKL mRNAs. This suggested that the hypoxia-induced elevation of C/EBPβ and RANKL mRNAs was dependent on the HIF-1 activity. PDL cells transfected with a specific small interfering RNA designed to target the C/EBPβ gene showed a significant suppression of the RANKL mRNA. These findings indicated that C/EBPβ may play an important role in tooth root resorption via RANKL activation in hypoxia-exposed PDL cells.

著者

Takashi Kifune Hisanori Ito Misa Ishiyama Satoko Iwasa Hiroki Takei Tomokazu Hasegawa Masatake Asano Tetsuo Shirakawa

出版者

Nihon University School of Dentistry

雑誌

Journal of Oral Science (ISSN:13434934)

巻号頁・発行日

vol.60, no.4, pp.519-525, 2018 (Released:2018-12-27)

参考文献数

32

被引用文献数

11

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Hypoxia induces complex cellular responses that are mediated by a key transcription factor, hypoxia-inducible factor-1 (HIF-1). HIF-1 promotes production of cytokines and angiogenic factors and contributes to recovery of injured tissues. In the present study, expressions of angiogenin (ANG) and vascular endothelial growth factor (VEGF), which are potent angiogenic factors in mammalian tissues, were examined in immortalized fibroblasts exposed to hypoxia. After 24 h of exposure to hypoxia, ANG and VEGF mRNAs expressions were significantly elevated in periodontal ligament (PDL) fibroblasts but not in embryonic fibroblasts. Hypoxia also increased productions of ANG and VEGF proteins in PDL fibroblasts. HIF-1α mRNA expression was not affected by hypoxia in either fibroblast, although HIF-1α protein expression was enhanced after exposure to hypoxia. Treatment of PDL fibroblasts with dimethyloxaloylglycine, a prolyl hydroxylase inhibitor that stabilizes the HIF-1α protein, significantly increased expressions of ANG and VEGF mRNAs under normoxia. This suggests that stabilization of HIF-1α is crucial for upregulation of ANG and VEGF in PDL fibroblasts. These results indicate that, under hypoxic conditions, HIF-1α upregulates synthesis of ANG and VEGF in PDL fibroblasts and promotes angiogenesis.