Détails sur le projet
Description
The major cause of tooth loss after the age of 35 is periodontal
disease. The goal of periodontal therapy is stated as providing a
dentition that will function in health and comfort for the life of the
patient. This goal of providing a functional dentition has led to the
development of varied approaches to therapy to preserve the
periodontium. Recent reports indicate that this is an achievable goal
and that the dentition can be maintained in a healthy functional state.
Regeneration of the periodontium is defined as reproduction of
reconstitution of a lost or injured part. The biochemical and molecular
biological events necessary for regeneration to occur have not been
defined. During the last two years we have actively studied biochemical
manipulation of dentin surfaces with matrix factors and polypeptide
growth factors to try and establish the appropriate conditions to induce
periodontal regeneration. These studies indicate that periodontal
ligament cells primarily respond chemotactically to TGFBeta and bFGF
whereas PDGF is a major mitogenic stimulus. This response is not
uniform. Depending on the age of donor we observed low to high
responders with "young" donors responding substantially better than
"old" donors. We observed a decrease in biological response of primary
cultures of PDL cells as they are detached and reattached for passage in
culture. Further evidence indicates that unattached cells express
different molecular biological markers when compared to attached cells.
We have observed decreases in specific mRNAs for fibronectin, actin, c-
myc, bFgf and PDGF. Addition of PDL-CTX induces a PDL cell phenotype
which is consistent with an increased chemotactic and mitogenic response
characteristic of young donors. Here we propose to continue to
characterize the factors necessary to induce PDL cells to assume a young
migratory and mitogenic phenotype. Additionally, we will examine the
interaction of various peptides with PDL cells that result in increased
or decreased expression of mRNAs for factors necessary for cell survival
and proliferation. The interaction of PDL-CTX and bFGF, PDGF and
TGFBeta will be examined in relationship to the expression of FN, actin,
c-myc, c-sis and c-fos. We will next establish the phenotype
characteristic of the "young" PDL cells. This will be compared and
contrasted to aging cultures of PDL cells or "old" primary cultures of
PDL cells. Receptor number and affinity for various polypeptides in
addition to expression of mRNAs will be determinants. We will also
investigate the cell-cell relationship between endothelial cells (which
synthesize and secrete bFGF) and PDL cells.
From our studies we hypothesize that as PDL cells age in vitro or in
vivo they become less responsive to specific matrix and polypeptide
growth factors. We further hypothesize that "old" PDL cells do not
synthesize and secrete adequate concentrations of PDL-CTX to maintain a
non senescent phenotype. Finally, as both endothelial cells and PDL
cells become more refractive to growth factor stimulation (decrease in
angiogenesis and healing potential) the formerly health periodontium
becomes susceptible to disease.
Statut | Terminé |
---|---|
Date de début/de fin réelle | 9/15/87 → 9/29/95 |
Financement
- National Institute of Dental and Craniofacial Research
Keywords
- Bioquímica
- Parodontología
- Biología celular
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