Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05765942 |
| Other study ID # |
534622 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
December 1, 2023 |
Study information
| Verified date |
March 2023 |
| Source |
University of Baghdad |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Peri-implantitis is a non-linear and accelerating pattern of loss of supporting bone tissue
associated with clinical signs of inflammation and increased probing depths compared to
baseline measurements. It can present as an asymptomatic condition with infection and fast
progression of bone resorption or clinically symptomatic with mucosal inflammation, redness,
edema, mucosal enlargement, bleeding on probing (BOP), suppuration, increased probing depth,
and radiographic bone loss. The host immune defense against bacterial challenge is
responsible for the damage, and the local immune-inflammatory process is associated with
disrupted bone remodeling. New studies looking for predictive and accurate early biomarkers
for this pathology have the utmost relevance. David Baltimore et al. proposed a feedback loop
involving miRNA-146a and TLR signaling, which has been shown to be up-regulated in
inflammatory diseases such as osteoarthritis and rheumatoid arthritis.
miRNA-146a and miRNA-155 were the first miRNAs identified to be induced in immune cells
stimulated by TLRs and proinflammatory cytokines. Precision medicine uses molecular research
and different biomarkers, population studies, and big data analysis to recreate complex
disease models. Several studies have compared the miRNA profiles of patients with
periodontitis with healthy patients. Although periodontitis and peri-implantitis share many
features, researchers' findings of periodontitis are not necessarily applicable to
peri-implantitis. In fact, based on emerging evidence, peri-implantitis, and periodontitis
exhibit several key differences, including their histopathological and molecular
characteristics. Considering the aforementioned analysis, inflammatory miRNAs may be
differentially expressed in peri-implantitis tissue compared with healthy gingival tissue.
This study will investigate the gene expression levels of miRNA-146a and miRNA-155 and their
correlation with inflammatory levels of their target genes in human gingival tissue
surrounding dental implants diagnosed with peri-implantitis and health.
Description:
MiRNAs are small non-coding RNA molecules that are approximately 18-22 non-transcribed spacer
NTS long. These single-stranded molecules regulate gene expression by binding to the
complementary sequences in the 3-untranslated or coding region of the target mRNAs, leading
to either blockade of translation or induction of target mRNA degradation. Therefore, miRNAs
participate in not only physiological processes within cells and tissues but also
pathological processes. According to previous reports, miRNAs are specifically involved in
many inflammatory and bone-related diseases, such as rheumatoid arthritis, osteoporosis, and
periodontitis.
The miRNA-146 family is composed of two members, miRNA-146a and miRNA-146b that are located
on chromosomes 5 and 10, respectively. proposed a feedback loop involving miRNA-146a and TLR
signaling. They found the induction of transcription of miRNA-146a by lipopolysaccharide LPS,
tumor necrosis factor-alpha (TNFa) and interleukin-1b (IL-1b) is dependent on NF-kb, and that
in turn, miRNA-146a potentially targets tumor necrosis factor receptor-associated family
(TRAF6) and interleukin-1 receptor-associated kinase (IRAK1), implicating it as a negative
regulator fine-tuning the immune response. As stated, too strong or too prolonged induction of
the innate immune response can have detrimental effects resulting in acute and chronic
inflammatory disorders. The high expression of miRNA-146a is up-regulated in many inflammatory
diseases such as osteoarthritis and rheumatoid arthritis (RA), the latter involving
up-regulation following stimulation with inflammatory cytokines such as TNF-a and IL1-b.
Interestingly, a polymorphism in the 3-untranslated region (3-UTR) of the mRNA encoding the
miR-146a target IRAK1 is associated with susceptibility to Rheumatoid Arthritis and psoriatic
arthritis.
MiRNA-146a and miRNA-155 were the first miRNAs identified to be induced in immune cells
stimulated by TLRs and proinflammatory cytokines. In human and murine immune cells, miRNA-155
can be classified as an early response gene, since its expression is highly induced within 2 h
of TLR activation (TLR2, TLR3, TLR4, and TLR9). MiRNA-155 negatively regulates TLR-signaling
by targeting key signaling molecules, including TAB2, MyD88, and NF-kb subunit p65.
Overexpression of miRNA-155 suppresses the production of the proinflammatory cytokines IL-8
and TNF-a, whereas IL-10, which exerts anti-inflammatory properties, inhibits miR-155
expression to maintain homeostasis. MiR-155 also facilitates CXCL12 signaling through the
inhibition of SHIP-1, a negative regulator of TLR-induced signals. Moreover, SHIP-1
regulation by miR-155 controls the pathogenesis of experimental colitis, suggesting that
miR-155 can also have proinflammatory functions.
The advances made in proteomics, genomics, and molecular biology aid in the control and
treatment of the disease by taking advantage of precision or stratified medicine, i.e.
"segregating the individuals into subpopulations who vary in their disease susceptibility and
response to a precise treatment". Precision medicine uses molecular research and different
biomarkers, population studies, and big data analysis to recreate complex disease models. It
seems reasonable to expect that in the future, the accuracy, predictive values, and
advantages of these predictive models which include new molecular candidates could benefit
and improve the control of different multifactorial and complex diseases, such as
peri-implantitis. Indeed, this approach has been considerably developed in oncology and
genetic diseases, but it is still under progress in the dental field. Expanding the research
of new molecules and biomarkers in peri-implant tissues would allow us to monitor the
clinical status of the implants, to classify them as well as the patients according to their
real risk of developing biological complications. In this regard, an important class of gene
modulators that have been scarcely explored in the context of periimplantitis include miRNAs.
Several studies have compared the miRNA profiles of patients with periodontitis with healthy
patients. Although periodontitis and peri-implantitis share many features, researchers'
findings of periodontitis are not necessarily applicable to peri-implantitis. Based on
emerging evidence, peri-implantitis, and periodontitis exhibit several key differences,
including their histopathological and molecular characteristics. Considering the
aforementioned analysis, inflammatory miRNAs may be differentially expressed in
peri-implantitis tissue compared with healthy gingival tissue.
