Intermittent Force Induces High RANKL Expression in Human Periodontal Ligament Cells

Nakao, Kayoko; Goto, Tetsuya; Gunjigake, Kaori; Konoo, Tetsuro; Kobayashi, Shigeru; Yamaguchi, Kazunori

doi:10.1177/154405910708600708

Cited by 80 publications

(63 citation statements)

References 28 publications

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“…Compressive force significantly increases the expression of RANKL but decreases osteoprotegerin, a decoy receptor for RANKL, in human PDL fibroblasts (PDLFs) cultured in vitro in a time-and magnitude-dependent manner (Nishijima et al, 2006). It has also been demonstrated that intermittent force up-regulates RANKL expression via IL-1 in human PDLFs (Nakao et al, 2007). The results from these studies suggest that enhanced osteoclastogenesis in compression side PDLs may be partly caused by compressive force-induced RANKL expression in PDLFs.…”

Section: Introductionsupporting

confidence: 48%

“…Subsequently, osteoclast differentiation may be induced by the additive actions of RANKL and VEGF. In addition to hypoxia, compressive force also up-regulates RANKL expression in PDLFs (Kanzaki et al, 2002;Nakao et al, 2007), suggesting that in compression side PDLs, RANKL expression is strongly induced by both compressive force and local hypoxia. Given that hypoxia-induced HIF-1α down-regulates osteoprotegerin expression in chondrocytes (Shirakura et al, 2010), the ratio of RANKL to osteoprotegerin may be increased in compression side PDLs, creating favorable conditions for osteoclastogenesis.…”

Section: A B Cmentioning

confidence: 99%

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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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Section: Introductionsupporting

confidence: 48%

Section: A B Cmentioning

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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“…[17][18][19][20][21][22][23][24][25][26] Among the manner of mechanical stress, compressive stress was used to confirm the role of PDL cell in the tissue remodeling process of the compressive side during orthodontic tooth movement with particular focus on osteoclastogenesis. Hydrostatic compression, 22,23 reverse-tension compression, 24 and direct contact compression methods 19,25,26 were used to provide compressive stress on cultured cells. The direct contact compression method appeared to mimic most in vivo systems in orthodontic treatment because a static compressive force is applied to the tooth in daily orthodontic practice and that PDL tissue is compressed directly between two hard structures, bone and cementum.…”

Section: Discussionmentioning

confidence: 99%

Effects of compressive stress on the expression of M-CSF, IL-1β, RANKL and OPG mRNA in periodontal ligament cells

et al. 2009

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Objective: The aim of this study was to determine if human PDL cells can produce osteoclastogenic mRNA and examine how compressive stress affects the expression of osteoclastogenic mRNA in human PDL cells. Methods: Human PDL cells were obtained from biscupids extracted for orthodontic treatment. The compressive force was adjusted by increasing the number of cover glasses. PDL cells were subjected to a compressive force of 0.

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“…The cytokines are produced by cells in the periodontal tissue as fibroblasts and osteoblasts, and they participate in normal physiological bone turnover and remodeling [11][12][13][14][15][16][17]. Many characteristics of these cytokines are of interest in orthodontics, since cytokines in the GCF reflect the microenvironment of periodontal tissues, in which orthodontic forces are applied [2,4,15]. Several studies also revealed that cytokines are fundamental in cell signaling in bone [14,18,19] and in mediating mechanically induced bone remodeling (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…The actions of cytokines include several effects on immune cells and modulation of inflammatory responses [10,11]. The cytokines are produced by cells in the periodontal tissue as fibroblasts and osteoblasts, and they participate in normal physiological bone turnover and remodeling [11][12][13][14][15][16][17]. Many characteristics of these cytokines are of interest in orthodontics, since cytokines in the GCF reflect the microenvironment of periodontal tissues, in which orthodontic forces are applied [2,4,15].…”

Section: Introductionmentioning

confidence: 99%

Cytokines in crevicular fluid and orthodontic force: a systematic review

Allgayer

Menezes

Rinaldi

2017

Rev. Odonto Ciênc. (Online)

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OBJECTIVE: This paper aimed to analyze studies in the literature addressing the role of cytokines in the gingival crevicular fluid (GCF) in the orthodontic treatment. METHODS: Several databases were surveyed using both MESH terms and free terms. Additional studies were obtained by reference tracking. This review was registered in PROSPERO, and the procedures foreseen by its statement were followed. Data were obtained from the included studies addressing the orthodontic mechanics, GCF sampling/handling methods, and cytokine measurements. Clinical studies written in English were browsed. Papers were selected by one reviewer and checked by a second investigator. RESULTS: A total of 115 articles were identified, among which 25 were selected for detailed analysis. Common drawbacks consisted mainly of inadequacies in the study design (e.g. short duration and small number of study subjects). The most consistent result was a peak of cytokine levels at 1 d. Associations were observed between prostaglandin E2 (PGE2) and interleukin-1β (IL-1β) and pain, velocity of tooth movement, and treatment mechanics. Interleukin-1b and PGE2 showed different patterns of up-regulation, with IL-1β being more responsive to mechanical stress and PGE2 more responsive to synergistic regulation of IL-1β and mechanical force. The results support the use of light continuous forces for orthodontic treatment. CONCLUSION: There was a tendency of maintenance of relatively high IL-1β levels for longer periods with the use of light continuous forces, which might decrease the frequency of activation. These outcomes provide evidence at the cellular level for the utilization of light continuous forces.Key words: Systematic review; Orthodontics, corrective; Gingival Crevicular Fluid (GCF); Interleukin; T Cells.Papel das citocinas presentes no fluido crevicular durante o tratamento ortodôntico: uma revisão sistemática REsUMO OBJETIVO: Este artigo teve como objetivo analisar estudos na literatura abordando o papel das citocinas no Líquido do Sulco Gengival no tratamento ortodôntico. MéTODOS: Várias bases de dados foram pesquisadas usando termos MESH e termos livres. Estudos adicionais foram obtidos por rastreamento de referência. Esta revisão foi registrada no PROSPERO, e os procedimentos previstos por sua declaração foram seguidos. Os dados foram obtidos dos estudos incluídos sobre a mecânica ortodôntica, métodos de amostragem / manuseio de Líquido do Sulco Gengival e medições de citoquinas. Estudos clínicos escritos em inglês foram pesquisados. Os trabalhos foram selecionados por um revisor e verificados por um segundo investigador. RESULTADOS: Foram identificados 115 artigos, dentre os quais 25 foram selecionados para análise detalhada. As desvantagens comuns consistiram principalmente em insuficiências no design do estudo (por exemplo, curta duração e pequeno número de sujeitos do estudo). O resultado mais consistente foi um pico de níveis de citocinas a 1 d. Foram observadas associações entre prostaglandina E2 (PGE2) e interleucina-1β (IL-1β) ...

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Intermittent Force Induces High RANKL Expression in Human Periodontal Ligament Cells

Cited by 80 publications

References 28 publications

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

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

Effects of compressive stress on the expression of M-CSF, IL-1β, RANKL and OPG mRNA in periodontal ligament cells

Cytokines in crevicular fluid and orthodontic force: a systematic review

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