Tooth, Impacted Clinical Trial
Official title:
The Role of Matrix Metalloproteinases in Orthodontic Treatment
The purpose of this study is to test whether the two MMPs can be up-regulated during orthodontic treatment. Alveolar bone samples will be collected from partially impacted third molars after orthodontic uprighting for different periods of time in volunteers.
Long treatment time is a major factor causing high fees for orthodontic treatment. Patients
would have dental caries or periodontitis resulting from improper oral hygiene care during
this long treatment period. How to speed up the tooth movement which determines the duration
of orthodontic treatment, can help more people to obtain good occlusion and esthetics.
Orthodontic force on a tooth induces bone resorption on the compression side and bone
deposition on the tension side, thus the bone remodels and then the tooth moves. Therefore,
bone resorption is the rate-limiting step of a lengthy orthodontic treatment.
Bone resorption is a complex process. The mineral component is dissolved by acid from
osteoclasts. On the other hand, the organic components are digested with proteolytic enzymes
secreted from osteoblasts and osteoclasts. We focus on our study on specific proteases which
can digest extracellular matrix, called matrix metalloproteinases (MMPs). Osteoblast-derived
MMPs play an important role during initiation of bone resorption. However, the mechanism of
its regulation is not clear. The past studies applied stretching or tension on single layer
of cultured cells to characterize cellular response to the mechanical stimulation. Now we
simulate part of the bone resorption process by cultivating osteocyte-like cells in
three-dimensional collagen gel under periodical compression.
In a preliminary study, we focus on transcriptional changes of MMPs upon compression in an
osteosarcoma cell line MG-63. Initial data form microarray indicated specific increase of
two MMPs expression after one day of compression. This increased expression was specific
because the levels of house-keeping genes (ex. Beta-actin or GAPDH) and bone-specific
markers were unaltered. Therefore, we proposed that increased MMP expression of osteoblasts
under compression is the first step for bone remodeling switching from synthesis to
degradation of osteoid. In order to test this hypothesis, the following specific aims will
be achieved:
1. To test whether these two MMPs can be up-regulated during orthodontic treatment.
Alveolar bone samples will be collected from partially impacted third molars after
orthodontic uprighting for different periods of time in volunteers. In situ
hybridization and immunohistochemistry analysis for MMPs will reveal their roles in
this physiological process.
2. To optimize the regulation by changing the magnitude and frequency of the pressure, and
characterize the time table for these changes.
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Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind, Primary Purpose: Treatment
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