The Role of Matrix Metalloproteinases (MMPs) in Orthodontic Tooth Movement
Condition: Tooth, Impacted; Molar, Third
MeSH terms: Tooth, Impacted
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Orthodontic treatment
Intervention type(s): Procedure
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: Single
Primary purpose: Treatment
Keywords: orthodontic tooth movement; matrix metalloproteinase; Orthodontics