Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement

Kanzaki, Hiroyuki; Chiba, Momoko; Arai, K.; Takahashi, Ichiro; Haruyama, Naoto; Nishimura, Makoto; Mitani, Hideo

doi:10.1038/sj.gt.3302707

Cited by 155 publications

(104 citation statements)

References 28 publications

(32 reference statements)

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“…Using an in vivo gene transfer approach, molar movement was decreased by 47.8% (p<0.001) after 3 weeks of twice weekly OPG plasmid DNA injections [14]. In contrast to RANKL plasmid DNA injections that resulted in 31.6% (p<0.01) more molar movement [13]. These two gene therapy studies showed the potential of directly targeting this pathway in altering tooth movement.…”

Section: Discussionmentioning

confidence: 95%

“…It has also been demonstrated that excess OPG actually impairs bone remodeling in a situation such as callus repair following fracture indicating that the ideal ratio of OPG to RANKL is dependent on the mechanical model being employed [12]. Finally, local OPG gene transfer to sites significantly diminishes while RANKL gene transfer significantly enhances orthodontic tooth movement possibly by respectively inhibiting or enhancing RANKL-mediated osteoclastogenesis [13,14]. Orthodontic tooth movement is a well-utilized in vivo model for determining the contributions of various exogenous and endogenous agents to mechanically mediated bone modeling [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement

Dunn

Park

Kostenuik

et al. 2007

Bone

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement

Dunn

Park

Kostenuik

et al. 2007

Bone

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“…Linkage disequilibrium was shown between orthodontic ERR and a marker for the TNFRSF11A gene (Al-Qawasmi et al, 2003b), encoding RANK, a receptor essential for RANKL-mediated osteoclastogenesis. Although RANKL gene transfer has been shown to increase tooth movement (Kanzaki et al, 2006), RANKL levels have also been linked to severe orthodontic ERR . Another focus of research is OPG (osteoprotegerin), a decoy receptor that competes with RANKL to bind RANK, which when bound leads to suppression of osteoclast differentiation and activation, also inducing apoptosis.…”

Section: Biological Factors In Rate Of Tooth Movement and Errmentioning

confidence: 99%

“…Another focus of research is OPG (osteoprotegerin), a decoy receptor that competes with RANKL to bind RANK, which when bound leads to suppression of osteoclast differentiation and activation, also inducing apoptosis. OPG gene transfer to the PDL was shown to inhibit tooth movement and osteoclast differentiation (Kanzaki et al, 2006;Kanzaki et al, 2004;. Although PGE1 seems to increase the rate of tooth movement and root resorption (Lee, 1990;Spielmann, Wieslander & Hefti, 1989;Yamasaki, Shibasaki & Fukuhara, 1983;Yamasaki et al, 1984;Zhang, 1992), some of the PGE2 effects in orthodontics are still controversial.…”

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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“…While this has not been formally demonstrated in the clinic, animal studies strongly support this notion. For example, orthodontic tooth movement in a mouse model was accelerated by overexpressing Receptor Activator of Nuclear Factor Kappa B-Ligand (RANKL) (Kanzaki et al, 2006). RANKL promotes the formation and bone resorptive activity of osteoclasts, the specialized cells charged with bone resorption (Hofbauer and Heufelder, 2001).…”

Section: Introductionmentioning

confidence: 99%