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

Abstract：

INTRODUCTION:The RANKL-OPG axis is a key regulator of osteoclastogenesis and bone turnover activity. Its contribution to bone resorption under altered mechanical states, however, has not been fully elucidated. Here we examined the role of OPG in regulating mechanically induced bone modeling in a rat model of orthodontic tooth movement. METHODS:The maxillary first molars of male Sprague-Dawley rats were moved mesially using a calibrated nickel-titanium spring attached to the maxillary incisor teeth. Two different doses (0.5 mg/kg, 5.0 mg/kg) of a recombinant fusion protein (OPG-Fc), were injected twice weekly mesial to the first molars. Tooth movement was measured using stone casts that were scanned and magnified. Changes in bone quantity were measured using micro-computed tomography and histomorphometric analysis was used to quantify osteoclasts and volumetric parameters. Finally, circulating levels of TRAP-5b (a bone resorption marker) was measured using enzyme-linked immunosorbent assay. RESULTS:The 5.0 mg/kg OPG-Fc dose showed a potent reduction in mesial molar movement and osteoclast numbers compared to controls (p<0.01). The molar movement was inhibited by 45.7%, 70.6%, and 78.7% compared to controls at days 7, 14, and 21 respectively, with the high dose of OPG. The 0.5 mg dose also significantly (p<0.05) inhibited molar movement at days 7 (43.8%) and 14 (31.8%). While incisor retraction was also decreased by OPG-Fc, the ratio of incisor to molar tooth movement was markedly better in the high-dose OPG group (5.2:1, p<0.001) compared to the control group (2.3:1) and the low-dose OPG group (2.0:1). CONCLUSIONS:Local delivery of OPG-Fc inhibits osteoclastogenesis and tooth movement at targeted dental sites.

journal_name

Bone

journal_title

Bone

authors

Dunn MD,Park CH,Kostenuik PJ,Kapila S,Giannobile WV

doi

10.1016/j.bone.2007.04.194

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

446-55

issue

3

eissn

8756-3282

issn

1873-2763

pii

S8756-3282(07)00373-0

journal_volume

41

pub_type

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