Local OPG Gene Transfer to Periodontal Tissue Inhibits Orthodontic Tooth Movement - Corrective Dentistry (Orthodontics) Articles

Local OPG Gene Transfer to Periodontal Tissue Inhibits Orthodontic Tooth Movement
2004
H. Kanzaki1,*, M. Chiba2, I. Takahashi1, N. Haruyama2, M. Nishimura1, and H. Mitani1
Journal of Dental Research

© 2004 International and American Associations for Dental Research

1 Division of Orthodontics and Dentofacial Orthopedics, and 2 Division of Oral Dysfunction Science, Department of Oral Health and Development Sciences, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan;

* corresponsing author, kanzaki@mail.tains.tohoku.ac.jp

ABSTRACT

Previously, we discovered that RANKL expression is induced in compressed periodontal ligament cells, and that this promotes osteoclastogenesis on the compression side in orthodontic tooth movement. We hypothesized that local OPG gene transfer to the periodontium would neutralize the RANKL activity induced by mechanical compressive force, thereby inhibiting osteoclastogenesis and diminishing tooth movement. The upper first molars of six-week-old male Wistar rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of functional OPG protein was confirmed in vitro. The inactivated HVJ envelope vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the palatal periodontal tissue of upper first molars. When this local OPG gene transfer was performed, OPG production was induced, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly diminished tooth movement. In this study, we report that OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.

KEY WORDS: gene transfer Ô osteoprotegerin Ô tooth movement Ô mechanical stress Ô osteoclastogenesis

INTRODUCTION

Orthodontic tooth movement occurs during the bone remodeling sequence that is induced by therapeutic mechanical stress (Roberts et al., 1981). Osteoclasts form on the compressed side of an orthodontically moving tooth and resorb the alveolar bone, changing the position of the tooth (Storey, 1973; Davidovitch, 1988; Brudvik and Rygh, 1994). It has been reported that osteoclastogenesis is primarily activated by the receptor activator of nuclear factor kappa B ligand (RANKL) and inhibited by osteoprotegerin (OPG) (Simonet et al., 1997; Udagawa et al., 1999; Yasuda et al., 1999). Previously, we discovered that periodontal ligament (PDL) cells, which exist between teeth and alveolar bone, induce osteoclastogenesis in vitro through the up-regulation of RANKL expression via PGE2 synthesis when subjected to mechanical-compressive force (Kanzaki et al., 2002). Furthermore, it has been reported that RANKL expression was induced on the compressed side of an orthodontically moving tooth (Oshiro et al., 2002). Combining this information, we hypothesized that local OPG induction at the compressive site of the periodontium might neutralize the RANKL activity induced by the mechanical compressive force, inhibiting osteoclastogenesis and diminishing orthodontic tooth movement.

To test our hypothesis, we used experimental tooth movement in rats with or without local OPG gene transfer via a hemagglutinating virus of Japan (HVJ; Sendai virus) envelope vector gene delivery system.

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