<i>In situ</i> expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue

Ogasawara, T.; Yoshito, Yoshimine; Kiyoshima, Tamotsu; Kobayashi, Ieyoshi; Matsuo, Kazuki; Akamine, A; Sakai, Hiroshi

doi:10.1111/j.1600-0765.2004.00699.x

Cited by 106 publications

(81 citation statements)

References 29 publications

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“…These results suggest that the inhibition of HIF-1 transcriptional activity and VEGF expression is also involved in antioxidant-induced retardation of orthodontic tooth movement through the down-regulation of osteoclastogenesis and subsequent bone resorption. Receptor activator of nuclear factor-κB ligand (RANKL) is an essential factor for osteoclastogenesis, and RANKL expression is up-regulated in the compression side of PDL tissues (Ogasawara et al, 2004;Wada et al, 2006). RANKL expression was also up-regulated by hypoxia in PDLFs, and antioxidants diminished hypoxia-induced RANKL expression in PDLFs in vitro and in the rat PDL tissues in vivo [data not shown, Park et al (in press)].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Antioxidants on the Production of Pro-Inflammatory Cytokines and Orthodontic Tooth Movement

Chae

Park

Hwang

et al. 2011

Molecules and Cells

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Orthodontic force causes gradual compression of the periodontal ligament tissues, which leads to local hypoxia in the compression side of the tissues. In this study, we investigated whether antioxidants exert a regulatory effect on two factors: the expression of pro-inflammatory cytokines in human periodontal ligament fibroblasts (PDLFs) that were exposed to mechanical compression and hypoxia and the rate of orthodontic tooth movement in rats. Exposure of PDLFs to mechanical compression (0.5-3.0 g/cm 2 ) or hypoxic conditions increased the production of intracellular reactive oxygen species. Hypoxic treatment for 24 h increased the mRNA levels of IL-1β, IL-6 and IL-8 as well as vascular endothelial growth factor (VEGF) in PDLFs. Resveratrol (10 nM) or N-acetylcysteine (NAC, 20 mM) diminished the transcriptional activity of hypoxiainducible factor-1 and hypoxia-induced expression of VEGF. Combined treatment with mechanical compression and hypoxia significantly increased the expression levels of IL-1β, IL-6, IL-8, TNF-α and VEGF in PDLFs. These levels were suppressed by NAC and resveratrol. The maxillary first molars of rats were moved mesially for seven days using an orthodontic appliance. NAC decreased the amount of orthodontic tooth movement compared to the vehicletreated group. The results from immunohistochemical staining demonstrated that NAC suppressed the expression of IL-1β and TNF-α in the periodontal ligament tissues compared to the vehicle-treated group. These results suggest that antioxidants have the potential to negatively regulate the rate of orthodontic tooth movement through the down-regulation of pro-inflammatory cytokines in the compression sides of periodontal ligament tissues.

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Section: Discussionmentioning

confidence: 99%

The Effect of Antioxidants on the Production of Pro-Inflammatory Cytokines and Orthodontic Tooth Movement

Chae

Park

Hwang

et al. 2011

Molecules and Cells

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“…These cytokines induce recruitment of endothelial cells (monocytes) that differentiate into osteoclasts after binding of RANKL (receptor activator of nuclear factor kappa ligand), an osteoclast differentiation factor (Ogasawara et al, 2004). On the ERR side, an animal study and one clinical association study revealed that absence or a mutant gene (less transcribed) of IL1-β are respectively linked to increase in orthodontic ERR Al-Qawasmi et al, 2003a).…”

Section: Biological Factors In Rate Of Tooth Movement and Errmentioning

confidence: 99%

Orthodontic mechanotransduction and the role of the P2X7 receptor

Viecilli

Katona

Chen

et al. 2009

American Journal of Orthodontics and Dentofacial Orthopedics

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DEDICATIONTo my parents, who have supported my education. iv ACKNOWLEDGMENTSOne of the most important things I have learned during my PhD is the necessity of the existence of a working network of people that can help you achieve your goals. The more effectively this network functions, the higher the chance you will achieve the goals quickly.I would first like to thank my parents, who have unconditionally supported my decision to abandon a profitable private practice in Orthodontics, and return to humble student conditions while aiming for a full time academic career.I also thank my girlfriend Laura Kruter who has (almost always) been ok with my, some might say, not very sane ideas. Sometimes they do turn out fine, though (like this "PhD" one).I can hardly think of anyone else that could have complemented my work and ideas during this Program as well as Dr. Thomas Katona. While I was passionately conditioned to an idea, he was always rational and careful. While I was sometimes furious with a shortcoming, he was always temperate and humorous. When I ran into his office with some news about a project, he would always listen and almost never seem too busy to see me. While I was working and something went wrong, he would listen and wonder with me about the "whys" and "hows", instead of telling me what to do or express disappointment. He was even subject to some of my home culinary experiments. I was extremely fortunate to find someone that thought about science the same way I did, and that actually helped me with my project instead of just telling me what to do. I felt like we worked as a team, and that helped to increase my motivation during my studies. The third part of this project tested the role of the P2X7 receptor in the dentoalveolar morphology of C57B/6 mice. P2X7R KO (knockout) mice were compared to C57B/6 WT to identify differences in a maxillary molar and bone. Tooth dimensions viii were measured and 3D bone morphometry was conducted. No statistically significant differences were found between the two mouse types. P2X7R does not have a major effect on alveolar bone or tooth morphology.The final part examines the role of the P2X7 receptor in a controlled biomechanical model. Orthodontic mechanotransduction was compared in wild-type (WT) and P2X7R knock-out (KO) mice. Using Finite Element Analysis, mouse mechanics were scaled to produce typical human stress levels. Relationships between the biological responses and the calculated stresses were statistically tested and compared.There were direct relationships between certain stress magnitudes and root resorption and bone formation. Hyalinization and root and bone resorption were different in WT and KO. Orthodontic responses are related to the principal stress patterns in the PDL and the P2X7 receptor plays a significant role in their mechanotransduction.

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“…RANKL induces osteoclast differentiation from hematopoietic precursors and stimulates the bone-resorbing activity of osteoclasts (Suda et al, 1999;Udagawa et al, 1999). It has been reported that continuous compression up-regulates RANKL expression in rat PDL in vivo (Ogasawara et al, 2004). 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).…”

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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In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue

Cited by 106 publications

References 29 publications

The Effect of Antioxidants on the Production of Pro-Inflammatory Cytokines and Orthodontic Tooth Movement

The Effect of Antioxidants on the Production of Pro-Inflammatory Cytokines and Orthodontic Tooth Movement

Orthodontic mechanotransduction and the role of the P2X7 receptor

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

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