Emerging therapeutic strategies targeting bone signaling pathways in periodontitis.

Periodontitis is a multifactorial immune-mediated disease exacerbated by dysregulated alveolar bone homeostasis. Timely intervention is crucial for disease management to prevent tooth loss. To successfully manage periodontitis, it is imperative to understand the cellular and molecular mechanisms involved in its pathogenesis to develop novel treatment modalities. Non-surgical periodontal therapy (NSPT) such as subgingival instrumentation/debridement has been the underlying treatment strategy over the past decades. However, new NSPT approaches that target key signaling pathways regulating alveolar bone homeostasis have shown positive clinical outcomes. This narrative review aims to discuss endogenous bone homeostasis mechanisms impaired in periodontitis and highlight the clinical outcomes of preventive periodontal therapy to avoid invasive periodontal therapies. Although the anti-resorptive therapeutic adjuncts have demonstrated beneficial outcomes, adverse events have been reported. Diverse immunomodulatory therapies targeting the osteoblast/osteoclast (OB/OC) axis have shown promising outcomes in vivo. Future controlled randomized clinical trials (RCT) would help clinicians and patients in the selection of novel preventing therapies targeting key molecules to effectively treat or prevent periodontitis.

Downregulation of miRNA-26 in chronic periodontitis interferes with innate immune responses and cell migration by targeting phospholipase C beta 1.

AIM: To evaluate the potential role of miR-26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization. MATERIALS AND METHODS: Expression of miR-26a-5p and miR-26b-5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non-surgical (scaling and root planing) therapy by RT-qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation. Cytokine expression was assessed in miR-26a-5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans or Pg lipopolysaccharide (LPS). Wound closure assays were performed in cells transfected with miR-26a-5p, while the impact on cytoskeletal organization was assessed by F-actin staining. RESULTS: miR-26a-5p and miR-26b-5p were downregulated in diseased gingiva and restored 4-6 weeks post-therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase C beta 1 as a bona fide novel target exhibiting antagonistic expression pattern in disease and post-therapy cohorts. miR-26a-5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement. CONCLUSIONS: Downregulated miR-26a-5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defence and wound healing.

Association between ridge morphology and complexity of implant placement planning in the posterior mandible.

STATEMENT OF PROBLEM: Uncertainties regarding the 3D ridge morphology of the posterior mandible can greatly increase the risk of surgical complications during dental implant placement. By using cone beam computed tomography (CBCT) imaging and a computer-guided implant treatment software program before any invasive procedure, it is possible to assess ridge morphology and understand the surgical complexity and risk level. PURPOSE: The purpose of this radiological clinical study was to evaluate a large series of CBCT images to evaluate ridge shape variations along posterior mandibular edentulous regions and to clarify their associations with the level of implant planning complexity. MATERIAL AND METHODS: One hundred and twenty CBCT files were analyzed retrospectively for a total 240 hemimandibular sites. Images of each edentulous region of the mandibular first and second premolar and first and second molar sites were evaluated in the sagittal plane. Ridge morphology and implant planning complexity per site were assessed. Categorical variables were presented as number of events and percentages. The chi-square test was used to compare the categorical variables (P=.05). RESULTS: Of 491 partially edentulous mandibular sites, 235 were on the right, and 256 were on the left. Forty-two sites had a distal adjacent tooth, while 266 sites had no distal adjacent tooth. The sagittal bone sections demonstrated oblique (40.53%), straight (31.77%), S-shape (24.24%), hourglass (2.44%), and basal bone (1.02%) ridge morphologies. Implant complexity was deemed straightforward in 66.19% of sites, while 31.6% were identified as advanced and 2.54% as complex. When ridge morphology was evaluated from straight to basal-round bone shape, the implant complexity followed the same trend of change from a straightforward to complex procedure (P=.001) for edentulous second and first molar regions. No significant differences were noted at edentulous second premolar sites (P=.063). The missing second molar sites with oblique morphology were predicted to have 60.9% straightforward complexity, and first molar sites with oblique morphology had 55.8% straightforward implant complexity. Second premolars with straight ridge morphology had 71.7% straightforward complexity, whereas first premolars with the same shape had 92.5% straightforward implant complexity. CONCLUSIONS: Careful evaluation of sagittal CBCT images can provide significant clinical information regarding ridge shape and anticipated surgical complexity before and at the time of implant placement. Surgical complexity is greatest at the most posterior mandibular edentulous sites, and extra attention and caution should be exercised during the surgical planning phases of implant surgery.

Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects.

AIM: To evaluate human and herpesvirus-encoded microRNA (miRNA) expression in healthy and diseased gingiva of obese and non-obese subjects and compare the impact of localized and systemic inflammation on human miRNA profiles. MATERIAL AND METHODS: Healthy and inflamed gingival biopsies were collected from obese and non-obese subjects. Human and herpesvirus miRNA expression was quantified using quantitative PCR. Predicted targets of dysregulated miRNAs were identified using bioinformatics analysis, validated by dual luciferase assays and their expression assessed in healthy and diseased tissues. RESULTS: Our results show differential expression of miRNAs in both diseased groups compared to healthy counterparts. MMP-16 is identified as a novel target of miRNAs altered in disease. Expression analysis of genes predicted as target of differentially expressed miRNAs show significant changes in disease compared with healthy tissues. Finally, quantitation of four herpesvirus-derived viral miRNAs show that the expression and prevalence of herpesvirus miRNAs in diseased gingiva of obese subjects. CONCLUSION: Our findings show that miRNA (both cellular and virus) expression is differentially responsive to local and systemic inflammation. Some of these miRNAs can modulate key cellular genes with direct consequences on inflammatory pathways suggesting their impact on oral tissue transcriptome and functions.

microRNAs: Emerging players in oral cancers and inflammatory disorders.

Association of oral diseases and disorders with altered microRNA profiles is firmly recognized. These evidences support the potential use of microRNAs as therapeutic tools for diagnosis, prognosis, and treatment of various diseases. In this review, we highlight the association of altered microRNA signatures in oral cancers and oral inflammatory diseases. Advances in our ability to detect microRNAs in human sera and saliva further highlight their clinical value as potential biomarkers. We have discussed key mechanisms underlying microRNA dysregulation in pathological conditions. The use of microRNAs in diagnostics and their potential therapeutic value in the treatment of oral diseases are reviewed.

miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells.

Micro-RNAs (miRNAs) are small noncoding RNAs that regulate various biological pathways. As their role in phagocytosis remains poorly understood, we investigated their impact on phagocytosis in myeloid inflammatory cells. Seven miRNAs (miR-24, -30b, -101, 142-3p, -652-3p, -652-5p, and -1275) that were differentially expressed during monocyte to macrophage (Mφ) and monocyte to dendritic cell (DC) differentiation were screened for their potential role in phagocytosis. Among these, overexpression of miR-24, miR-30b, and miR-142-3p in human monocyte-derived Mφ, DC, monocytes, and PBMCs significantly attenuate phagocytosis of Escherichia coli and Staphylococcus aureus, as well as the secretion of inflammatory mediators, including TNF-α, IL-6, and IL-12p40. miRNA-mediated changes in cytokine profiles were observed at transcriptional and/or posttranscriptional levels and importantly exhibit miRNA-specific impact. To examine the underlying mechanism, we monitored the expression of phagocytosis pathway-associated genes and identified several genes that were altered in Mφ and DC transfected with miR-24, miR-30b, and miR-142-3p mimics. Some of these genes with altered expression also harbor putative miRNA binding sites. We show that miR-142-3p directly regulates protein kinase Cα (PKCα), a key gene involved in phagocytosis. Interestingly, miR-142-3p and PKCα exhibit antagonistic expression during Mφ and DC differentiation. Short interfering RNA-mediated knockdown of PKCα in Mφ leads to reduced bacterial uptake, further highlighting the role of the gene in phagocytosis. Overall, these results demonstrate that miR-24, miR-30b, and miR-142-3p regulate phagocytosis and associated cytokine production in myeloid inflammatory cells through modulation of various genes involved in the pathway.

MiRNA-Target Interaction Reveals Cell-Specific Post-Transcriptional Regulation in Mammalian Cell Lines.

MicroRNAs are 18-22 nucleotides long, non-coding RNAs that bind transcripts with complementary sequences leading to either mRNA degradation or translational suppression. However, the inherent differences in preferred mode of miRNA regulation among cells of different origin have not been examined. In our previous transcriptome profiling studies, we observed that post-transcriptional regulation can differ substantially depending on the cell in context. Here we examined mechanistic differences in the regulation of a let-7a targeted (wild type) or resistant (mutant) engineered renilla transcript across various mammalian cell lines of diverse origin. Dual luciferase assays show that compared to mutant (mut), the reporter gene containing wild type (wt) let-7a binding sites was efficiently suppressed upon transfection in various cell lines. Importantly, the strength of miRNA regulation varied across the cell lines. Total RNA analysis demonstrates that wt renilla mRNA was expressed to similar or higher levels compared to mut suggesting that translation repression is a predominant mode of miRNA regulation. Nonetheless, transcript degradation was observed in some cell lines. Ago-2 immunoprecipitation show that miRNA repressed renilla mRNA are associated with functional mi-RISC (miRNA-RNA induced silencing complex). Given the immense potential of miRNA as a therapeutic option, these findings highlight the necessity to thoroughly examine the mode of mRNA regulation in order to achieve the beneficial effects in targeting cells.

Osteoblastic and cytokine gene expression of implant-adherent cells in humans.

OBJECTIVES: Implant surface topography is a key determinant affecting osteoblastic differentiation and cell-cell signaling of implant-adherent cells. MATERIALS AND METHODS: To assess the early osteoinductive and cell-cell signaling events in adherent cells, commercially pure titanium implants (2.2 × 5 mm) with nanotopography (HF-treated TiO2 grit-blasted) were compared with micron-scale topography TiO2 grit-blasted (micron-scale, control) implants in vivo. Six implants (n = 3/surface) were placed in 10 systemically healthy subjects and removed by reverse threading at 1, 3, and 7 days. Gene expression profiles of adherent cells were interrogated using low-density RT-PCR arrays. RESULTS: Osteoinduction was not observed at day 1 on either surface. At 3 days, elevated levels of BMP6, osteopontin, and osterix (OSX) were observed in RNA of cells adherent to both micron-scale and nanotopography surfaces. Both surfaces supported osteoinductive gene expression at 7 days; however, modest elevations of most mRNAs and significantly higher OSX mRNA levels were measured for cells adhered to nanotopography implants. Further, chemokine and cytokine profiles including CXCL10, CXCL14, IL-9, IL-22, and TOLLIP were upregulated on nanotopographic surfaces as compared with microtopographic surfaces. CONCLUSIONS: Implants with superimposed nanoscale topography generate a greater induction of genes linked to osteogenesis and cell-cell signaling during the early phases of osseointegration.

Early molecular assessment of osseointegration in humans.

OBJECTIVE: To determine the early temporal-wide genome transcription regulation by the surface topography at the bone-implant interface of implants bearing microroughened or superimposed nanosurface topology. MATERIALS AND METHODS: Four commercially pure titanium implants (2.2 × 5.0 mm) with either a moderately roughened surface (TiOblast) or super-imposed nanoscale topography (Osseospeed) were placed (n = 2/surface) in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole-genome microarray using the Affymetrix Human gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces. RESULTS: There were no significant differences when comparing the two implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix (ECM), collagen fibril organization, and angiogenesis were upregulated at both surfaces (day7 vs. day3). Abundant upregulation of several differential markers of alternative activated macrophages was observed (e.g., MRC1, MSR1, MS4A4A, SLC38A6, and CCL18). The biological processes involved with the inflammatory/immune response gene expression were concomitantly downregulated. CONCLUSIONS: Gene regulation implicating collagen fibrillogenesis and ECM organization as well as the inflammatory/immune responses involving the alternative activated pathway are observed in implant adherent cells at early (3-7 days) after implantation. These gene expression events may indicate a pivotal role of collagen fibrillogenesis as well as immunomodulation in altering bone accrual and biomechanical physical properties of the implant-bone interface.

Leukocyte production of inflammatory mediators is inhibited by the antioxidants phloretin, silymarin, hesperetin, and resveratrol.

Antioxidants possess significant therapeutic potential for the treatment of inflammatory disorders. One such disorder is periodontitis characterised by an antimicrobial immune response, inflammation, and irreversible changes to the supporting structures of the teeth. Recognition of conserved pathogen-associated molecular patterns is a crucial component of innate immunity to Gram-negative bacteria such as Escherichia coli, as well as the periodontal pathogen Aggregatibacter actinomycetemcomitans. In this study, we investigated the antioxidants Phloretin, Silymarin, Hesperetin, and Resveratrol to ascertain whether they altered the production of inflammatory mediators by innately-activated leukocytes. Peripheral blood mononuclear cells were stimulated with lipopolysaccharide purified from Aggregatibacter actinomycetemcomitans, and the production of cytokines, chemokines, and differentiation factors was assayed by enzyme-linked immunosorbent assay, cytometric bead array, and RT-PCR. Significant inhibition of these factors was achieved upon treatment with Phloretin, Silymarin, Hesperetin, and Resveratrol. These data further characterise the potent anti-inflammatory properties of antioxidants. Their ability to inhibit the production of inflammatory cytokines, chemokines, and differentiation factors by a heterogeneous population of leukocytes has clear implications for their therapeutic potential in vivo.

Are healing abutments being reused in periodontics residency programs in the United States? A survey-based study.

PURPOSE: Recent studies indicate that reusing healing abutments (HAs) may pose a risk of biomaterial cross contamination among patients. The intent is to investigate whether postgraduate periodontics residency programs in the United States are reusing dental implant HAs and determine if there is a standardization in the decontamination and sterilization protocol of used HAs. METHODS: An electronic survey consisting of-seven multiple choice and/or short answer questions pertaining to the re-use of HAs among postdoctoral periodontics programs was sent to program directors of 57 accredited dental schools in the United States via an online survey system (Qualtrics). Three follow-up remainder emails were sent to programs that did not respond after over a 6-month period. Data were analyzed using descriptive statistics. RESULTS: Of the 57 postdoctoral periodontics program directors contacted, only 14 responded with three programs (3/14, 21%) reported reusing HAs. Approximately, 46% stated their residents place dental implants in two stages, while ∼54% stated they used a one-stage protocol indicating varied time exposure of HA to the oral cavity. Even in a two-stage protocol, the extended time HA remained in situ varied from 4 weeks to 6 months. Each program reusing HAs employed a distinct decontamination approach highlighting a notable lack of standardization in practices. CONCLUSION: The findings from our study suggest that a minority of residency programs in the United States are reusing HAs. However, the limited number of responses leaves uncertainty regarding whether our findings underestimate the prevalence of this practice and accurately reflect the reality. Among those re-using HAs, there seems to be a lack of standardization in their decontamination, potentially leading to cross-contamination of residual biomaterial among patients.

Dynamic changes in macrophage polarization during the resolution phase of periodontal disease.

AIM: Polarization of macrophages (Mφ) is a well-controlled axis with considerable consequences in both the pro-inflammatory and resolution phases of inflammation. We aimed to determine if periodontal therapy may instigate M1 to M2 Mφ polarization favoring resolution of inflammation within periodontal tissues. METHODS: Gingival biopsies were excised from subjects diagnosed with Stage III, Grade B periodontitis before and 4-6 weeks after nonsurgical periodontal therapy. Total RNA was isolated and pro- and anti-inflammatory markers associated with Mφ polarization assessed by RT-qPCR. Mice were subject to ligature-induced periodontitis and gingival tissues collected after 8 days in-situ or 10 days after ligature removal and M1 and M2 Mφ markers examined by RT-qPCR and flow cytometry. RESULTS: In human samples, improvement in clinical parameters posttherapy correlates with reduced bacterial burden, downregulation in M1 (TNF-α, STAT1, CXCL10, and miR-155), and elevated levels of M2 (STAT6, TGM2, CCL22, and IL-10) Mφ markers. In a murine model of resolution of LIP, we observed reduced levels of M1 Mφ markers cox2, iNOS2, F4/80+CD80+, and F4/80+CD86+ and elevated levels of M2-like Mφ markers tgm2, arg1, F4/80+CD206+ and F4/80+CD163+ corroborated human findings. CONCLUSION: Resolution of periodontal inflammation is associated with M1 to M2 Mφ polarization after nonsurgical periodontal therapy. Assessment of Mφ markers can provide relevant clinical information on the successful response of periodontal therapy and may be used to target nonresponders.

Dynamic Changes in Macrophage Polarization during the Resolution Phase of Periodontal Disease.

Periodontal inflammation is largely governed by infiltration of myeloid cells, in particular macrophages. Polarization of Mφ within the gingival tissues is a well-controlled axis and has considerable consequences for how Mφ participate in inflammatory and resolution (tissue repair) phases. We hypothesize that periodontal therapy may instigate a pro-resolution environment favoring M2 Mφ polarization and contribute towards resolution of inflammation post-therapy. We aimed to evaluate the markers of macrophage polarization before and after periodontal therapy. Gingival biopsies were excised from human subjects with generalized severe periodontitis, undergoing routine non-surgical therapy. A second set of biopsies were excised after 4-6 weeks to assess the impact of therapeutic resolution at the molecular level. As controls, gingival biopsies were excised from periodontally healthy subjects, undergoing crown lengthening. Total RNA was isolated from gingival biopsies to evaluate pro- and anti-inflammatory markers associated with macrophage polarization by RT-qPCR. Mean periodontal probing depths, CAL and BOP reduced significantly after therapy and corroborated with the reduced levels of periopathic bacterial transcripts after therapy. Compared to heathy and treated biopsies, higher load of Aa and Pg transcripts were observed in disease. Lower expression of M1Mφ markers (TNF-α, STAT1) were observed after therapy as compared to diseased samples. Conversely, M2Mφ markers (STAT6, IL-10) were highly expressed in post-therapy as opposed to pre-therapy, which correlated with clinical improvement. These findings corroborated with murine ligature-induced periodontitis and resolution model, comparing the respective murine Mφ polarization markers (M1 Mφ: cox2 , iNOS2 and M2 Mφ: tgm2 and arg1 ). Our findings suggest that imbalance in M1 and M2 polarized macrophages by assessment of their markers can provide relevant clinical information on the successful response of periodontal therapy and can be used to target non-responders with exaggerated immune responses.

Assessment of Detoxification Strategies for Used Dental Implant Healing Abutments: Macroscopic and Biological Implications.

PURPOSE: Dental implant manufacturers recommend healing abutments (HA) be used for single-patient use; however, reuse on multiple patients following decontamination and sterilization is common. This study aims to evaluate four decontamination strategies utilizing enzymatic agents, available in most clinical settings, to determine the level to which biomaterial can be removed in a group of previously used HA (uHA). Secondly, to determine the degree to which the decontaminated HA are capable of inducing an inflammatory response in-vitro compared to new, never used HA. MATERIALS AND METHODS: Fifty HA were collected following 2-4 weeks of intraoral use and distributed randomly into 5 test groups (Group A-E; n = 10/group). Group A: Enzymatic cleaner foam + Autoclave; Group B: Ultrasonic bath with enzymatic cleaner + Autoclave; Group C: Prophy jet + Enzymatic cleaner foam + Autoclave; Group D: Prophy jet + ultrasonic bath with enzymatic cleaner + Autoclave; Group E: Prophy jet + Autoclave. Ten new, sterile HA served as controls (Group "Control"). Residual protein concentration was determined by a Micro BCA protein assay while HA from each group were stained with Phloxine B and macroscopically examined for the presence of debris. To examine the inflammatory potential, human primary macrophages were exposed to HA and supernatant levels of 9 cytokines/chemokines profiles were analyzed using a multiplex bead assay. RESULTS: All test groups presented with differences in the degree of visual decontamination compared to Controls, with Groups D and E displaying the most effective surface debris removaland reduced protein concentration. Of the detoxification strategies, Groups D and E removed the greatest biomaterial while least effective was Group A. However, compared to Controls, multiplex assays revealed high levels of inflammatory cytokine secretion up to 5 days from all Test Groups (A-E) irrespective of the decontamination method used. CONCLUSION: Our study found that compared to new, never used HA, decontamination of uHA utilizing enzymatic cleaners failed to reestablish inert HA surfaces and prevent an inflammatory immune response in-vitro. Clinicians should not reuse HA even after attempts to decontaminate and sterilize HA surfaces.

Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis.

In periodontitis, a common chronic inflammatory condition, gram-negative-rich bacterial biofilms trigger, in susceptible individuals, perpetuating inflammation that results in extensive tissue damage of tooth supporting structures. To delineate immune cell-dependent mechanisms whereby bacterial challenge drives persistent destructive inflammation in periodontitis and other inflammatory diseases, we studied involved tissues ex vivo and investigated host cell responses to the periodontal pathogen Porphyromonas gingivalis, in vitro. Diseased lesions were populated by abundant Th17 cells, linked to infection, chronic inflammation/autoimmunity and tissue pathology. In vitro, P. gingivalis, particularly the more virulent strain W83, stimulated myeloid antigen presenting cells (APC) to drive Th17 polarization. Supernatants from myeloid APC exposed to P. gingivalis were capable of enhancing Th17 but not Th1 polarization. P. gingivalis favored the generation of Th17 responses by stimulating the production of Th17 related cytokines IL-1ß, IL-6 and IL-23, but not Th1 related IL-12. By inducing NFκB activation, P. gingivalis promoted IL-1ß, IL-6 and IL-12p40 production, but not IRF3 phosphorylation, connected to generation of the IL-12p35 chain, ultimately restricting formation of the intact IL-12 molecule. Promotion of Th17 lineage responses was also aided by P. gingivalis proteases, which appeared to differentially degrade pivotal cytokines. In this regard, IL-12 was largely degraded by P. gingivalis, whereas IL-1ß was more resistant to proteolysis. Our data unveil multiple pathways by which P. gingivalis may orchestrate chronic inflammation, providing insights into interventional strategies.

Effect of laser on TNF-alpha expression in inflamed human gingival tissue.

This study sought to evaluate the effect of low-level laser treatment combined with scaling and root planing (SRP) on gingival tissue levels of TNF-alpha in subjects with periodontal disease. Eighty gingival papilla biopsy samples were obtained from 60 patients diagnosed with chronic advanced periodontitis; randomly assigned to three treatment groups (n = 20), as well as 20 subjects with no periodontal disease (group A). Group B received SRP on a single quadrant/day for four consecutive days. On day 5, all quadrants were rescaled. Groups C and D received the same treatment as group B plus laser application with the low-level diode laser (630-670 nm, 1.875 J/cm(2)) for five and ten consecutive days, respectively. Papilla biopsies were obtained from subjects and evaluated by ELISA for levels of TNF-alpha. The values in the control group were 5.2 ± 3.21 pg/mg and baseline values for the examined groups were 46.01 ± 16.69. Significantly decreased level of TNF-alpha for groups C and D was found after treatment, while group B demonstrated reduction of TNF-alpha of 31.34%. The results of this study show suppression of TNF-alpha in gingival tissue after low-level laser treatment as adjunct to SRP. Data may suggest beneficial anti-inflammatory effects of the laser treatment when used as adjunctive periodontal treatment.

Peri-implant disease education and diagnosis in the pre-doctoral curriculum.

PURPOSE: The purpose of this study was to assess how pre-doctoral periodontal programs in the United States of America are educating their dental students regarding the management of peri-implant diseases and secondarily, to determine if a current standard of teaching exists. METHODS AND MATERIALS: Electronic surveys were distributed to pre-doctoral program directors across 57 dental schools in the United States via a secure online survey system. The survey consisted of 19 questions pertaining to curriculum structure involving didactic and clinical management of peri-implant diseases. RESULTS: A total of 25 program directors (44%) responded, and data were analyzed using descriptive statistics. The results indicated a lack of standardization of pre-doctoral didactic and clinical curriculum among dental schools. CONCLUSIONS: Data pooled from 25 pre-doctoral periodontal programs in the United States show that there is currently no standardization in the dental school curriculum related to the didactic and clinical management of peri-implant diseases. The development of standardized content is recommended to assist program directors in assessing and enhancing educational experiences for dental students on the management of peri-implant diseases.

Human herpesvirus-encoded MicroRNA in host-pathogen interaction.

Human herpesviruses (HHV) are ubiquitous, linear dsDNA viruses that establish lifelong latency, disrupted by sporadic reactivation. HHV have evolved diverse ingenious mechanisms to evade robust host defenses. Incorporation of unique stem loop sequences that generate viral microRNAs (v-miRs) exemplifies one such evolutionary adaptation in HHV. These noncoding RNAs can control cellular and viral transcriptomes highlighting their ability in shaping host-HHV interactions. We summarize recent developments in functional characterization of HHV-encoded miRNAs in shaping the outcome of host-pathogen interaction. Non-immunogenic dissemination of v-miRs through exosomes confer added advantage to HHV in incessant modulation of host microenvironment. This review delineates the mechanistic role of v-miRs in facilitating viral persistence and tropism by targeting genes associated with cellular (apoptosis, angiogenesis, cell migration, etc.) and viral life cycle (latency, lytic and reactivation). Burgeoning evidences indicate plausible association of v-miRs in various immune-mediated diseases (nasopharyngeal carcinoma, neurological disorders, periodontal diseases, etc.) and herpesvirus-related malignancies indicating their broad-spectrum impact on host cellular pathways. We propose to exploit tisssue and systemic levels of v-miRs as diagnostic and prognostic markers for cancers and immune-mediated diseases. Therapeutic targeting of v-miRs will advance the promising outcomes of preclinical discoveries to bedside application.

Evidence-Based Clinical Outcomes of Immediate and Early Loading of Short Endosseous Dental Implants: A Meta-analysis.

PURPOSE: Short dental implants serve as a valuable alternative for patients with limited bone height. Immediate or early provisionalization facilitates a more physiologic environment for the gingival tissues to be modeled. The purpose of this meta-analysis was to systematically review and evaluate the implant survival and marginal bone loss with immediate and early loading protocols of short dental implants (≤ 6 mm). MATERIALS AND METHODS: A literature search (electronic and manual) was conducted to identify studies with a focused PICO question: "In patients with short dental implants, does loading time affect treatment outcomes?" Studies using an immediate or early loading protocol for restoration of short implants with a mean follow-up of at least 1 year, and refraining from the use of advanced surgical procedures (sinus floor elevation, bone augmentation), were included. After evaluating patient selection and outcome reporting biases, a meta-analysis was conducted to assess implant survival and bone loss for studies fulfilling the inclusion criteria. Bone loss differences between immediate and early loading protocols were evaluated by Student t test, and Spearman correlation analysis was used to analyze the trends between crown-to-implant (C/I) ratio and bone loss. RESULTS: A total of 396 studies with patients receiving short implants (≤ 6 mm) with immediate or early prosthetic loading protocols were identified. For the 7 included studies, the pooled implant survival rate for 322 implants with a follow-up ranging from 1 to 10 years (5 years) was 91.63% (95% CI: 88% to 94%), with a mean bone loss effect estimate of 0.52 ± 0.1 mm (z = 3.07, P < .002). The differences observed in the mean bone loss for studies using immediate loading as opposed to early loading were not statistically significant. A moderate but significant positive correlation was observed between the C/I ratio and mean bone loss levels (r = 0.67, P = .02). CONCLUSION: Short implants with immediate or early loading protocols have satisfactory long-term treatment prospects with satisfactory implant survival rates and minimal bone loss.

Rapid myeloid cell transcriptional and proteomic responses to periodontopathogenic Porphyromonas gingivalis.

Long-lived monocytes, macrophages, and dendritic cells (DCs) are Toll-like receptor-expressing, antigen-presenting cells derived from a common myeloid lineage that play key roles in innate and adaptive immune responses. Based on immunohistochemical and molecular analyses of inflamed tissues from patients with chronic destructive periodontal disease, these cells, found in the inflammatory infiltrate, may drive the progressive periodontal pathogenesis. To investigate early transcriptional signatures and subsequent proteomic responses to the periodontal pathogen, Porphyromonas gingivalis, donor-matched human blood monocytes, differentiated DCs, and macrophages were exposed to P. gingivalis lipopolysaccharide (LPS) and gene expression levels were measured by oligonucleotide microarrays. In addition to striking differences in constitutive transcriptional profiles between these myeloid populations, we identify a P. gingivalis LPS-inducible convergent, transcriptional core response of more than 400 annotated genes/ESTs among these populations, reflected by a shared, but quantitatively distinct, proteomic response. Nonetheless, clear differences emerged between the monocytes, DCs, and macrophages. The finding that long-lived myeloid inflammatory cells, particularly DCs, rapidly and aggressively respond to P. gingivalis LPS by generating chemokines, proteases, and cytokines capable of driving T-helper cell lineage polarization without evidence of corresponding immunosuppressive pathways highlights their prominent role in host defense and progressive tissue pathogenesis. The shared, unique, and/or complementary transcriptional and proteomic profiles may frame the context of the host response to P. gingivalis, contributing to the destructive nature of periodontal inflammation.