Expression of Hypoxia‐Inducible Factor‐1α in Human Periodontal Tissue

Ng, King-Tung; Li, Jingping; Ng, Kwong Man; Tipoe, George L.; Leung, W. Keung; Fung, Man-Lung

doi:10.1902/jop.2010.100100

Cited by 69 publications

(114 citation statements)

References 23 publications

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“…Hypoxia in oral cells/tissues is, in fact, a common occurrence [6]. The local hypoxic microenvironment is considered a consequence of growth/development, wound healing, smoking habits, or concurrent oral inlammation/infection/diseases.…”

Section: Hypoxia In the Oral/periodontal Environmentmentioning

confidence: 99%

“…The accumulation of intracellular HIF-1 promotes the transcription of a spectrum of genes to maintain cellular homeostasis. Hypoxia induces the expression of a number of angiogenic factors to improve the blood supply in needed areas including inlamed periodontium [6]. These include VEGF, platelet-derived growth factor (PDGF), and angioprotein-1 and -2.…”

Section: Hypoxia and Chronic Periodontal Inlammationmentioning

confidence: 99%

“…The tissue hypoxia in periodontal disease has been characterized by increased HIF-1α protein that is detectable in periodontitisafected tissue biopsies using Western blot and anti-HIF-1α immunostaining [6,30]. Myeloid cell lineage of HIF-1α -/-(deprived) mice had impaired immune efector molecules, such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) production, thus reducing their bactericidal capability [31].…”

Section: Hypoxia and Chronic Periodontal Inlammationmentioning

confidence: 99%

“…At the levels of tissues and cells, including the human periodontium, such adaptive responses to low oxygen tension or hypoxia are mainly mediated through a key cellular transcription factor named the hypoxia-inducible factor (HIF) [6].…”

Section: Introductionmentioning

confidence: 99%

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Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

Wang¹,

Chen²,

Leung³

2017

Hypoxia and Human Diseases

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Human periodontitis is a chronic inlammatory disease induced by opportunistic Gramnegative anaerobic bacteria at the tooth-supporting apparatus. Within the gingivitisafected sulcus or periodontal pocket, the resident anaerobic bacteria interact with the host inlammatory reactions leading to a lower oxygen or hypoxic environment. A cellular/tissue oxygen-sensing mechanism and its appropriate regulation are needed to assist tissue adaptation to natural/pathology-induced variations in oxygen availability. In this chapter, we reviewed the biological relevance of hypoxia in periodontal/oral cellular development, epithelial barrier function, periodontal inlammation, and immunity. The role of hypoxia-inducible factor-1α in pathogen-host cross talk and alveolar bone homeostasis was also discussed. The naturally occurring pathophysiological process of hypoxia appeared to entail fundamental relevance for periodontal defense and regeneration.

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Section: Hypoxia In the Oral/periodontal Environmentmentioning

confidence: 99%

Section: Hypoxia and Chronic Periodontal Inlammationmentioning

confidence: 99%

Section: Hypoxia and Chronic Periodontal Inlammationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

Wang¹,

Chen²,

Leung³

2017

Hypoxia and Human Diseases

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“…The presence of transforming growth factor (TGF-β) and vascular endothelial growth factor (VEGF) during periodontal disease is a consequence of endothelial damage and microcirculatory failure caused by inflammatory infiltrate (7). The basic fibroblast growth factor (bFGF) presents pro-angiogenic activity and its role is fundamental for satisfactory tissue repair (8).…”

Section: Introductionmentioning

confidence: 99%

Evolution of Periodontal Disease: Immune Response and RANK/RANKL/OPG System

et al. 2017

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The aim of this study was to evaluate markers of bone loss and immune response present in evolution of periodontal disease. One hundred and two Wistar rats were divided into three animals groups: PD0, without ligation and PD15 days and PD60 days, submitted to ligation placement with a sterile 3-0 silk cord in the cervical region of the upper first molar on both sides. Samples were obtained from the gingival tissue for histomorphometric analysis, immunohistochemical analysis of RANK, RANKL, OPG, characterization of the inflammatory infiltrate, quantification of nitric oxide, MCP-1, RANTES, IP10 chemokines, and expression of the TGF-β1, VEG, and bFGF. The number of inflammatory cells in gingival tissue was higher in PD60 samples. The collagen content and the area occupied by birefringent collagen fibers were lower for PD60. Differential leukocyte counting showed that there was a significantly higher polymorphonuclear influx in group PD15, while PD60 showed a greater number of lymphocytes. PD60 showed higher RANTES, IP-10, MCP-1 gene transcripts, as well as a higher nitric oxide concentration. Clinical evaluation revealed that the PD60 group presented an increase in furcal area. In conclusion, in this animal model the increase of RANK/RANKL and HGF markers is related to a specific immune response, and probably contributed to the evolution of periodontal disease. Investigating the effect of these biomarkers can help in targeted therapy for bone resorption, since blocking these can inhibit bone loss.

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HIF‐2 Inhibition Supresses Inflammatory Responses and Osteoclastic Differentiation in Human Periodontal Ligament Cells

Bae

Shin

Kang

et al. 2015

J of Cellular Biochemistry

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Recent reports suggest that hypoxia inducible factor-2α (HIF-2α) is a key regulator of osteoarthritis cartilage destruction. However, the precise role of HIF-2α in the inflammatory response and osteoclast differentiation remains unclear. The purpose of this study was to investigate the effect of HIF-2α on inflammatory cytokines, extracellular matrix (ECM) destruction enzymes, and osteoclastic differentiation in nicotine and lipopolysaccharide (LPS)-stimulated human periodontal ligament cells (PDLCs). HIF-2α was upregulated in chronically inflamed PDLCs of periodontitis patients, and in nicotine- and LPS-exposed PDLC in dose- and time-dependent manners. HIF-2α inhibitor and HIF-2α siRNA attenuated the nicotine- and LPS- induced production of NO and PGE2 , upregulation of iNOS, COX-2, pro-inflammatory cytokines (IL-1β, TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-11, and IL-17), and matrix metalloproteinases (MMPs; MMP-1, -8, -13, -2 and -9), and reversed the effect on TIMPs (TIMP-1 and -2) in PDLCs. The conditioned medium produced by nicotine and LPS-treated PDLCs increased the number of TRAP-stained osteoclasts, TRAP activity and osteoclast-specific genes, which has been blocked by HIF-2α inhibition and silencing. HIF-2α inhibitor and HIF-2α siRNA inhibited the effects of nicotine and LPS on the activation of Akt, JAK2 and STAT3, ERK and JNK MAPK, nuclear factor-κB, c-Jun, and c-Fos. Taken together, this study is the first to demonstrate that HIF-2α inhibition exhibits anti-inflammatory activity through the inhibition of inflammatory cytokines and impairment of ECM destruction, as well as blocking of osteoclastic differentiation in a nicotine- and periodontopathogen-stimulated PDLCs model. Thus, HIF-2α inhibition may be a novel molecular target for therapeutic approaches in periodontitis.

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Expression of Hypoxia‐Inducible Factor‐1α in Human Periodontal Tissue

Abstract: HIF-1α is expressed in healthy and diseased periodontium and may be related to TNF-α and VEGF function during periodontitis.

Cited by 69 publications

References 23 publications

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

Evolution of Periodontal Disease: Immune Response and RANK/RANKL/OPG System

HIF‐2 Inhibition Supresses Inflammatory Responses and Osteoclastic Differentiation in Human Periodontal Ligament Cells

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