Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05832541 |
| Other study ID # |
535622 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 18, 2022 |
| Est. completion date |
September 2024 |
Study information
| Verified date |
December 2023 |
| Source |
University of Baghdad |
| Contact |
Talib A Alnajaty |
| Phone |
009647707905702 |
| Email |
taleb.ali1105a[@]codental.uobaghdad.edu.iq |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Peri-implantitis is an inflammation of bacterial etiology characterized by inflammation of
mucous membranes and bone loss around the dental implant. A specific dental plaque bacteria
could stimulate host cells, including the junctional epithelium, to secrete a range of
pro-inflammatory cytokines involved in initiating the epithelial-mesenchymal transition (EMT)
process. EMT has been described as the transdifferentiation of epithelial cells into motile
mesenchymal cells.
Moreover, cytokines and bacterial products have been highlighted as EMT-predisposing factors.
The EMT process could render epithelial cells to lose their cell-cell adhesion and cell
polarity that lend these cells to lose their function as an integrated epithelial barrier.
E-cadherin is a calcium-dependent cell adhesion molecule that establishes cell-cell adhesion
that plays a critical role in maintaining a barrier function in the human epithelium,
including gingiva. The loss of E-cadherin is one of the most common biological indicators for
EMT. In contrast, vimentin is an intermediate filament expressed in mesenchymal cells and is
a canonical marker for EMT, which also promotes cell motility and an invasive phenotype.
It is largely reported that EMT is regulated by various transcriptional factors such as Snail
Family Transcriptional Repressor SNAIL1 and SNAIL2, zinc-finger E-box-binding (ZEB)1 and ZEB2
and TWIST transcription factors that suppress epithelial marker genes, and activate genes
related with the mesenchymal phenotype.
Recently, in vivo study has investigated the level of EMT markers in the gingival tissues of
periodontitis patients. It was found that the expression of E-cadherin was downregulated
while vimentin expression was upregulated.
Despite the similarities and differences between the pathogenesis of periodontal and
peri-implant diseases, the role of dental biofilm in the etiopathogenesis of the
aforementioned diseases was studied largely. While it is now accepted that EMT may
potentially play a role in periodontal disease pathogenicity, the possible role of EMT in the
disintegration of the peri-implant epithelial barrier and the pathogenesis of peri-implant
disease has not yet been investigated.
Description:
Dental implant therapy is a reliable treatment for replacing missing or lost teeth. Despite
its high survival and success rates, it has long been realized that biological complications
could occur in osseointegrated implants, collectively termed peri-implant diseases.
Peri-implantitis is the second most common form of peri-implant disease, and its prevalence
was shown to be 10% to 30% at the implant level and 20% at the patient level.
Peri-implantitis is an inflammation of bacterial etiology characterized by inflammation of
mucous membranes and bone loss around the dental implant. Clinically, it shows signs of
inflammation, bleeding on probing and/or suppuration, increased probing depths, and/or
recession of the mucosal margin in addition to radiographic bone loss compared to previous
examinations.
Inflammatory peri-implant lesions usually start due to the accumulation of bacterial plaque
and progress in a faster pattern compared to periodontitis.
It has been reported that specific dental plaque bacteria could stimulate host cells,
including the junctional epithelium, to secrete a range of pro-inflammatory cytokines
involved in initiating the epithelial-mesenchymal transition (EMT) process. EMT has been
described as the transdifferentiation of epithelial cells into motile mesenchymal cells. It
is considered integral in the development, wound healing, and stem cell behavior and
contributes pathologically to fibrosis and cancer progression.
Moreover, cytokines and bacterial products have been highlighted as EMT-predisposing factors.
It has been proposed that the EMT process could render epithelial cells to lose their
cell-cell adhesion and cell polarity that lend these cells to lose their function as an
integrated epithelial barrier. Consequently, bacterial invasion into the underlying
connective tissues could occur, and epithelial cells are assumed to have a mesenchymal cell
phenotype through the upregulation of mesenchymal markers and downregulation of epithelial
markers.
E-cadherin is a calcium-dependent cell adhesion molecule that establishes cell-cell adhesion,
known as the adherens junction, playing a critical role in maintaining a barrier function in
the human epithelium, including gingiva. The loss of E-cadherin is one of the most common
biological indicators for EMT. In contrast, vimentin is an intermediate filament expressed in
mesenchymal cells and is a canonical marker for EMT, which also promotes cell motility and an
invasive phenotype. It has been shown that the level of vimentin protein expression is
significantly increased by P. gingivalis infection.
It is largely reported that EMT is regulated by various transcriptional factors such as Snail
Family Transcriptional Repressor SNAIL1 and SNAIL2, zinc-finger E-box-binding (ZEB)1 and ZEB2
and TWIST transcription factors that suppress epithelial marker genes, and activate genes
related with the mesenchymal phenotype. These transcriptional factors act as E-cadherin
repressors and play a pivotal role in development, fibrosis, and cancer. Several signaling
pathways collaborate in the beginning and advancement of EMT, and they can promote SNAIL1
expression and transforming growth factor beta.
Recently, in vivo study has investigated the level of EMT markers in the gingival tissues of
periodontitis patients. It was found that the expression of E-cadherin was downregulated
while vimentin expression was upregulated. Accordingly, the authors proposed that EMT may
potentially play an essential role in the pathogenesis and prognosis of periodontal disease.
Much of the etiology and pathogenesis of peri-implant disease was acknowledged to be similar
to periodontitis since both share many clinical and radiologic features in common for
destructive inflammatory diseases. However, in contrast to periodontitis, peri-implantitis
lesions show a poorer vascular supply, a lack of connective tissue encapsulation of large
inflammatory cell infiltrates, and a differing cell profile with high numbers of B cells,
osteoclasts, and neutrophils. This suggests that peri-implantitis has a similar
aetiopathogenesis to periodontitis but also notable differences; its progression seems faster
and more aggressive.
Despite these similarities and differences between the pathogenesis of periodontal and
peri-implant diseases, the role of dental biofilm in the etiopathogenesis of the
aforementioned diseases was studied largely. While it is now accepted that EMT may
potentially play a role in periodontal disease pathogenicity, the possible role of EMT in the
disintegration of the peri-implant epithelial barrier and the pathogenesis of peri-implant
disease has not yet been investigated.
