Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05403164 |
| Other study ID # |
241621 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 12, 2021 |
| Est. completion date |
August 30, 2022 |
Study information
| Verified date |
May 2022 |
| Source |
University of Baghdad |
| Contact |
Saif S Saliem, MSc |
| Phone |
+964 7901529484 |
| Email |
drsaifjuma[@]codental.uobaghdad.edu.iq |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Periodontitis is a chronic inflammatory disease results is destruction of the attachment
apparatus of the teeth and ultimately tooth loss.
Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that
influence a polarized epithelial cell to undergo molecular/morphological changes leading to
acquisition of mesenchymal cell phenotype. This process is responsible for suppressing
epithelial-phenotype and it is known to be triggered by chronic exposure to inflammatory
cytokines, Gram-negative bacteria, hypoxia, smoking, and hyperglycemia.
Both periodontitis and EMT share common risk factors/promoters; however, the role of EMT in
the pathogenesis of periodontitis is not fully elucidated yet. Potential induction of EMT
within periodontal pockets may disrupt epithelial barrier thus facilitating invasion of
pathogenic periodontal pathogens to deeper tissues resulting in further tissue breakdown and
non-resolving periodontal lesion.
Description:
Periodontitis is a highly prevalent inflammatory disease affecting the attachment apparatus
of the teeth, leading to progressive destruction of periodontal ligament and resorption of
alveolar bone which if not treated, at early stages, it will lead to tooth loss. It is
characterised by presence of a wide diversity of pathogenic bacteria, specifically
Gram-negative anaerobes, that possess range of virulence factors responsible for triggering
intense inflammatory response. Although this response is protective in nature; however, it
leads to undesirable collateral damage to the surrounding tissues that is further aggravated
by the aberrant immune response of the host.
Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that
influence a polarized epithelial cell to undergo molecular/morphological changes leading to
acquisition of mesenchymal cell phenotype. EMT is modulated by range of regulatory pathways;
mainly, downstream of TGF-β signaling activity which is evident in many developmental and
pathological situations in which EMT is reported, including embryogenesis, inflammation and
tumor metastasis. The hallmark of TGFβ signaling is up-regulation of Snail, an E-cadherin
repressor. Overexpression of Snail has been found in various fibrotic diseases, including
liver fibrosis and renal fibrosis.
E-cadherin is a calcium-dependent homophilic cell adhesion molecule expressed on the cell
surfaces of epithelium and is a critical structure for stratification of squamous epithelia.
The significant reduction in E-cadherin expression observed in the gingival epithelium during
pocket formation and is believed to contribute to the pathogenesis of periodontal disease.
Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal
cells. IF, along with tubulin-based microtubules and actin-based microfilaments, comprises
the cytoskeleton. All IF proteins are expressed in a highly developmentally-regulated
fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this,
vimentin is often used as a marker of mesenchymal-derived cells or cells undergoing EMT
during both normal development and metastatic progression.
β-catenin is a dual function protein, involved in regulation and coordination of cell-cell
adhesion and gene transcription. β-catenin also acts as a morphogen in later stages of
embryonic development. Together with TGF-β, an important role of β-catenin is to induce a
morphogenic change in epithelial cells. It induces them to abandon their tight adhesion and
assume a more mobile and loosely associated mesenchymal phenotype.
Role of EMT on compromising epithelial barrier function of periodontal pocket lining is not
fully elucidated yet. Reported risk factors of EMT including prolonged exposure to cytokines,
Gram-negative bacteria, tobacco and hypoxia are also relevant to periodontitis. Potential
induction of EMT within periodontal pockets may disrupt epithelial barrier thus facilitating
invasion of pathogenic periodontal pathogens to deeper tissues resulting in further tissue
breakdown and non-resolving periodontal lesion.
