Ignite Creation Date:
2024-05-06 @ 6:45 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05765942
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-03-17
First Post:
2023-03-01
Brief Title:
MicroRNAs and Cytokines in Peri-Implantitis Tissue
Sponsor:
University of Baghdad
Organization:
University of Baghdad
Study Overview
Official Title:
Expression of microRNAs 146a and 155 and Cytokines in the Tissue Surrounding Dental Implants Diagnosed With Peri-implantitis
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed 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 ie 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
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 ie 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None