Analysis of gene expression profiles in human periodontal ligament cells under hypoxia: The protective effect of CC chemokine ligand 2 to oxygen shortage

Kitase, Yukiko; Yokozeki, Masahiko; Fujihara, Shinji; Izawa, Takashi; Kuroda, Shingo; Tanimoto, Kotaro; Moriyama, Keiji; Tanaka, Eiji

doi:10.1016/j.archoralbio.2009.03.010

Cited by 18 publications

(22 citation statements)

References 35 publications

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“…[9] Compressive force reduces blood flow in the PDL and alveolar bone, causing local hypoxia. [31,32] The periodontium is particularly sensitive to hypoxia, and a series of pathological and physiological reactions to hypoxia lead to the reduction of tissue defenses. [33] Furthermore, hypoxia results in the decrease of redox potential, which leads to the gathering of anaerobes.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-regulated human periodontal ligament cells via Wnt/β-catenin signaling pathway

et al. 2017

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Background:The aim of this study is to investigate the effects of hypoxia on the proliferation, morphology, migration ability, hypoxia inducible factor (HIF) 1 (HIF-1) expression, and the relationship with Wnt/β-catenin signaling of human periodontal ligament cells (hPDLCs) in vitro.Methods:hPDLCs (4th passage) cultured by the tissue culture method were randomly assigned to slight (5% O2), severe hypoxia (1% O2) groups, and the control (21% O2) group, respectively. From 1st to 7th day, the optical density values were detected, and the growth curve was described. Wound healing assay was done to observe the migration ability of hPDLCs under various O2 conditions. Then reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of cementum-related genes and Wnt signaling pathway-related genes. Further, RT-qPCR, Western blot, and immunofluorescence staining method were constructed to show HIF expressions under different O2 concentrations in hPDLCs.Results:The growth rate of hPDLCs decreased with the reduction of O2 content by degree, and the morphology of hPDLCs changed in different O2 contents. Besides, hPDLCs migrate faster in 21% and 5% O2 than in 1% O2, and both the expressions of cementum-related genes and Wnt signaling pathway-related genes were raised under hypoxic conditions. In addition, with the reduction of O2 concentration, the messenger RNA and protein level expression of HIF were all increased, and HIF was gradually transported from cytoplasm into the nucleus and in 1% O2 concentration, it was mainly expressed in the nucleus.Conclusion:This finding demonstrated that hypoxia was capable of suppressing the proliferation and migration ability, changing the morphology of hPDLCs, and stabilizing HIF-1α against degradation and promoting its translocation to the nucleus. Meanwhile, hypoxia may regulate hPDLCs proliferation and cementogenic differentiation via Wnt/β-catenin signaling pathway, which may potentially provide a novel insight into the etiology and treatment of periodontal diseases.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-regulated human periodontal ligament cells via Wnt/β-catenin signaling pathway

et al. 2017

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“…Orthodontic forces result in the deformation of blood vessels and disarrangement of surrounding tissues. Subsequently, blood flow and periodontal tissue adapt to the compression force, or when they fail, are responsible for cell death and tissue necrosis [57]. …”

Section: Pdl and Alveolar Bone Resorption And Remodelingmentioning

confidence: 99%

Periodontal Ligament and Alveolar Bone in Health and Adaptation: Tooth Movement

Jiang¹,

Guo²,

Chen³

et al. 2015

Tooth Movement

116

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The periodontal ligament (PDL) and alveolar bone are two critical tissues for understanding orthodontic tooth movement. The current literature is replete with descriptive studies of multiple cell types and their matrices in the PDL and alveolar bone, but is deficient with how stem/progenitor cells differentiate into PDL and alveolar bone cells. Can one type of orthodontic force with a specific magnitude and frequency preferably activate osteoblasts, whereas another force type activates osteoclasts? This chapter will discuss the biology of not only mature cells and their matrices in the periodontal ligament and alveolar bone, but also stem/progenitor cells that differentiate into fibroblasts, osteoblasts and osteoclasts. Key advances in tooth movement rely on further understanding of osteoblast and fibroblast differentiation from mesenchymal stem/progenitor cells, and osteoclastogenesis from the hematopoietic/monocyte lineage.

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“…Bone resorption is dominant on the compression side, whereas bone formation is dominant on the tension side (Cattaneo et al, 2005). Compressive force reduces blood flow in the PDL and alveolar bone, which leads to local hypoxia (Kitase et al, 2009;Kubota, 1989). Orthodontic tooth movement causes compression side PDLs to release various inflammatory mediators such as interleukin-1 (IL-1), tumor necrosis factor-α, IL-6 and prostaglandin E 2 (Kanzaki et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Periodontal Ligament Fibroblasts

Park

Baek

Lee

et al. 2011

Molecules and Cells

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During orthodontic tooth movement, local hypoxia and enhanced osteoclastogenesis are observed in the compression side of periodontal tissues. The receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/ stromal cell-derived factor that is essential for osteoclastogenesis. In this study, we examined the effect of hypoxia on RANKL expression in human periodontal ligament fibroblasts (PDLFs) to investigate the relationship between local hypoxia and enhanced osteoclastogenesis in the compression side of periodontal tissues. Hypoxia significantly enhanced the levels of RANKL mRNA and protein as well as hypoxia inducible factor-1α (HIF-1α) protein in PDLFs. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression in PDLFs under normoxic conditions, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL expression. To investigate further whether HIF-1α directly regulates RANKL transcription, a luciferase reporter assay was performed using the reporter vector containing the RANKL promoter sequence. Exposure to hypoxia or overexpression of constitutively active HIF-1α significantly increased RANKL promoter activity, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL promoter activity. Furthermore, mutations of putative HIF-1α binding elements in RANKL promoter prevented hypoxia-induced RANKL promoter activity. The results of chromatin immunoprecipitation showed that hypoxia or constitutively active HIF-1α increased the DNA binding of HIF-1α to RANKL promoter. These results suggest that HIF-1α mediates hypoxia-induced up-regulation of RANKL expression and that in compression side periodontal ligament, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in PDLFs.

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Analysis of gene expression profiles in human periodontal ligament cells under hypoxia: The protective effect of CC chemokine ligand 2 to oxygen shortage

Cited by 18 publications

References 35 publications

Hypoxia-regulated human periodontal ligament cells via Wnt/β-catenin signaling pathway

Hypoxia-regulated human periodontal ligament cells via Wnt/β-catenin signaling pathway

Periodontal Ligament and Alveolar Bone in Health and Adaptation: Tooth Movement

Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Periodontal Ligament Fibroblasts

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