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Research regarding Mechanism Elucidation of Tissue Remodeling Phenomena by Mechanical Stimulation

Research Outline

 In orthodontic treatment, teeth migration is considered to caused by the remodeling of supporting tissue (alveolar bone, periodontal membrane). This occurs as a result of bone resorption by osteoclastic cells on the side of the alveolar bone to which pressure is applied and bone addition by osteoblast cells on the side of the alveolar bone which is experiences pull. We are studying the kinetic change in periodontal ligament tissue, periodontal ligament cells, and osteoclastic cells located between the teeth and alveolar bone at that time.

Research Themes

  1. Research using three-dimensional cultured human cells of periodontal ligaments
  2. Effect of mechanical stimulation in an osteoclast differentiation induction system
  3. Research on periostin in mouse periodontal ligaments

1. Research using three-dimensional cultured human cells of periodontal ligaments

 In order to replicate an experimental system which more closely represents in vivo conditions, a three-dimensional model of cultured human cells of periodontal ligaments using collagen sponge was created and various types of mechanical pressure was applied. Research was carried out in order to identify the relationship between the change in expression level of cytokine genes responsible for osteoclast differentiation and the amount of applied pressure. As a result, it was found that when there is a high amount of pressure, periodontal ligament cells do not produce much cytokines that induce osteoclast differentiation. Therefore, a strong force is not considered necessary for optimum orthodontic force when moving teeth and a lower amount of pressure is recommended in orthodontic treatment.

Image of collagen sponge cell plug

Image of collagen sponge cell plug

2.Effect of mechanical stimulation in an osteoclast differentiation induction system

1. Analysis of an osteoclast differentiation induction system using a flexercell tension system

 Mechanical stimulation was applied to the differentiation process of osteoclastic cells, at a 10% cell extension rate and 30 cycles/min, using RAW264.7 cells which can be individually cultured to osteoclastic cells by adding RANKL. As a result, differentiation induction of the osteoclastic cells could be controlled, and differentiation/fusion of osteoclastic cells was quickly induced after its release. mRNA and proteins involved in the series of processes were measured, and analyzed at the gene level.

Flexercell tension system

Flexercell tension system

2. Analysis of an osteoclast differentiation induction system according to pressure

 The same differentiation induction system used in research theme 1 was used to search for the pressure stimulus. Various reactions were shown, depending on the pressure application method and the degree of applied pressure. There were patterns which showed a reduction in cells due to cell death unrelated to apoptosis and necrosis, and the existence of pressure which promotes differentiation induction of osteoclastic cells could also be clearly shown. We are analyzing the related factors of these reactions at the gene level.
According to these research themes, progress is being made in the research of the possibility that a mechanosensor can work for mechanical stimulation of osteoclastic cells alone.

Images of osteoclastic cell differentiation

Images of osteoclastic cell differentiation

3. Research on periostin in mouse periodontal ligaments

 Periostin is a new protein (Horiuchi, Amizuka et al., 1999) named after the fact that it is found in large quantities on periodontal ligaments and periosteum. Since periostin is produced in large quantities in tissues subjected to significant mechanical stress, its action in the periodontal membrane is assumed to be important. Hence in order to clarify the function of periostin in periodontal ligaments, paraffin tissue sections of the mandibular bones of a wild type mouse and periostin-/- mouse were prepared, and immunohistochemical analysis of the extracellular matrix, which contained periodontal membrane and its resolving enzymes, was performed. As a result, periostin is assumed to have the function of adjusting the localization of the extracellular matrix, and absence of periostin is thought to cause irregular periodontal ligament fibers and cell arrangement.

Image of wild-type mouse mandibular incisor

Image of wild-type mouse mandibular incisor

Image of a mandibular incisor of a non-periostin mouse

Image of a mandibular incisor of a non-periostin mouse