The role of the epithelial sentinels, Langerhans cells and γδT cells, in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) arises in the oral epithelium, a tissue in which immune surveillance is mediated by its primary resident leukocytes, Langerhans cells (LCs), and γδT cells. Under steady-state conditions, LCs and γδT cells play a critical role in maintaining oral mucosal homeostasis. As antigen-presenting cells of stratified epithelia, LCs respond to various challenges faced by the epithelium, orchestrating innate, and adaptive immune responses in order to resolve them. γδT cells also sense diverse epithelial insults and react rapidly through cytokine production and cytolytic activity. These epithelial sentinels are also considered to be the first leukocytes in the oral epithelium to encounter early carcinogenic events that have the potential of becoming OSCC. As evident in many malignancies, leukocyte populations help prevent cancer development although they also promote tumor progression. OSCC is no exception, as studies have reported both anti- and pro-tumor roles of LCs and γδT cells. In this review, we summarize the ontogeny of LCs and γδT cells in the oral epithelium and discuss their role in OSCC.

Periodontitis and Metabolic Syndrome: Statistical and Machine Learning Analytics of a Nationwide Study.

This study aimed to analyze the associations between periodontitis and metabolic syndrome (MetS) components and related conditions while controlling for sociodemographics, health behaviors, and caries levels among young and middle-aged adults. We analyzed data from the Dental, Oral, and Medical Epidemiological (DOME) record-based cross-sectional study that combines comprehensive sociodemographic, medical, and dental databases of a nationally representative sample of military personnel. The research consisted of 57,496 records of patients, and the prevalence of periodontitis was 9.79% (5630/57,496). The following parameters retained a significant positive association with subsequent periodontitis multivariate analysis (from the highest to the lowest OR (odds ratio)): brushing teeth (OR = 2.985 (2.739-3.257)), obstructive sleep apnea (OSA) (OR = 2.188 (1.545-3.105)), cariogenic diet consumption (OR = 1.652 (1.536-1.776)), non-alcoholic fatty liver disease (NAFLD) (OR = 1.483 (1.171-1.879)), smoking (OR = 1.176 (1.047-1.322)), and age (OR = 1.040 (1.035-1.046)). The following parameters retained a significant negative association (protective effect) with periodontitis in the multivariate analysis (from the highest to the lowest OR): the mean number of decayed teeth (OR = 0.980 (0.970-0.991)); North America as the birth country compared to native Israelis (OR = 0.775 (0.608-0.988)); urban non-Jewish (OR = 0.442 (0.280-0.698)); and urban Jewish (OR = 0.395 (0.251-0.620)) compared to the rural locality of residence. Feature importance analysis using the eXtreme Gradient Boosting (XGBoost) machine learning algorithm with periodontitis as the target variable ranked obesity, OSA, and NAFLD as the most important systemic conditions in the model. We identified a profile of the "patient vulnerable to periodontitis" characterized by older age, rural residency, smoking, brushing teeth, cariogenic diet, comorbidities of obesity, OSA and NAFLD, and fewer untreated decayed teeth. North American-born individuals had a lower prevalence of periodontitis than native Israelis. This study emphasizes the holistic view of the MetS cluster and explores less-investigated MetS-related conditions in the context of periodontitis. A comprehensive assessment of disease risk factors is crucial to target high-risk populations for periodontitis and MetS.

The efficacy of implant surface decontamination using chemicals during surgical treatment of peri-implantitis: A systematic review and meta-analysis.

AIM: To answer the following PICOS question: "In adult patients with peri-implantitis, what is the efficacy of surgical therapy with chemical surface decontamination of implant surfaces in comparison with surgical therapy alone or surgery with placebo decontamination, on probing pocket depth (PD) reduction and bleeding on probing (BoP)/suppuration on probing (SoP), in randomized controlled clinical trials (RCTs) and non-RCTs with at least 6 months of follow-up?" MATERIALS AND METHODS: Six databases were searched from their inception up to 20 May 2022. Data on clinical outcome variables were pooled and analysed using mean differences (MDs), risk ratios (RRs), or risk differences (RDs) as appropriate, 95% confidence intervals (CIs), and prediction intervals (PIs) in the case of significant heterogeneity. Primary outcomes were determined as changes in PD and BoP/SoP. Secondary outcomes were radiographic marginal bone loss (MBL), implant loss, and disease resolution. PROSPERO registration number: CRD42022325603. RESULTS: Six RCTs-two with moderate, three with high, and one with low risk of bias (RoB)-were included. These studies test the adjunctive effect of photodynamic therapy (PDT), chlorhexidine (CHX), and administration of local antibiotics (LAbs) during surgery on the clinical outcome. In a single 12-month study, the adjunctive use of local antibiotics showed a clinically relevant reduction of PD [MD = 1.44; 95%CI (0.40 to -2.48)] and MBL [MD = 1.21; 95%CI (0.44-1.98); one trial, 32 participants]. PDT showed a small but significant reduction in BoP [MD = 7.41%; 95%CI (0.81-14.00); p = 0.028; two trials; 42 participants]. Treatment with CHX resulted in no significant changes in PD, BoP, or MBL compared to placebo (saline solution). None of the interventions affected disease resolution and implant loss. Certainty of the evidence was very low for all outcome measures assessed. CONCLUSIONS: Within the limitations of this systematic review and the meta-analysis, adjunctive use of chemicals such as PDT, CHX, and LAbs for surface decontamination during surgery of peri-implantitis cannot be recommended as superior to standard debridement procedures (mechanical debridement with or without saline).

Early antitumor activity of oral Langerhans cells is compromised by a carcinogen.

Early diagnosis of oral squamous cell carcinoma (OSCC) remains an unmet clinical need. Therefore, elucidating the initial events of OSCC preceding tumor development could benefit OSCC prognosis. Here, we define the Langerhans cells (LCs) of the tongue and demonstrate that LCs protect the epithelium from carcinogen-induced OSCC by rapidly priming αßT cells capable of eliminating γH2AX+ epithelial cells, whereas γδT and natural killer cells are dispensable. The carcinogen, however, dysregulates the epithelial resident mononuclear phagocytes, reducing LC frequencies, while dendritic cells (DCs), macrophages, and plasmacytoid DCs (pDCs) populate the epithelium. Single-cell RNA-sequencing analysis indicates that these newly differentiated cells display an immunosuppressive phenotype accompanied by an expansion of T regulatory (Treg) cells. Accumulation of the Treg cells was regulated, in part, by pDCs and precedes the formation of visible tumors. This suggests LCs play an early protective role during OSCC, yet the capacity of the carcinogen to dysregulate the differentiation of mononuclear phagocytes facilitates oral carcinogenesis.

The efficacy of pocket elimination/reduction compared to access flap surgery: A systematic review and meta-analysis.

AIM: To assess the efficacy and adverse effects of resective surgery compared to access flap in patients with periodontitis. METHODS: Randomized controlled trials with a follow-up ≥6 months were identified in ten databases. Screening, data extraction, and quality assessment were conducted by two reviewers. The primary outcome was probing pocket depth, and the main secondary outcome was clinical attachment level. Data on adverse events were collected. Meta-analysis was used to synthesize the findings of trials. RESULTS: A total of 880 publications were identified. Fourteen publications from nine clinical trials met the inclusion criteria and were included for analysis. Meta-analysis was carried out using all available results. The results indicated superior pocket depth reduction following resective surgery compared to access flap after 6-12 months of follow-up (weighted mean difference 0.47 mm; confidence interval 0.7-0.24; p = .010). After 36-60 months of follow-up, no differences were found between the two treatments in pocket depth and attachment level. The prevalence of adverse effects was not different between the groups. Post-operative recession tended to be more severe for the resective approaches. CONCLUSION: Resective surgical approach was superior to access flap in reducing pocket depth 6-12 months post-surgery, while no differences between the two modalities were found at 36-60 months of follow-up.

Cell-intrinsic regulation of murine epidermal Langerhans cells by protein S.

AXL, a member of the TYRO3, AXL, and MERTK (TAM) receptor tyrosine kinase family, has been shown to play a role in the differentiation and activation of epidermal Langerhans cells (LCs). Here, we demonstrate that growth arrest-specific 6 (GAS6) protein, the predominant ligand of AXL, has no impact on LC differentiation and homeostasis. We thus examined the role of protein S (PROS1), the other TAM ligand acting primarily via TYRO3 and MERTK, in LC function. Genetic ablation of PROS1 in keratinocytes resulted in a typical postnatal differentiation of LCs; however, a significant reduction in LC frequencies was observed in adult mice due to increased apoptosis. This was attributed to altered expression of cytokines involved in LC development and tissue homeostasis within keratinocytes. PROS1 was then excised in LysM+ cells to target LCs at early embryonic developmental stages, as well as in adult monocytes that also give rise to LCs. Differentiation and homeostasis of LCs derived from embryonic precursors was not affected following Pros1 ablation. However, differentiation of LCs from bone marrow (BM) precursors in vitro was accelerated, as was their capability to reconstitute epidermal LCs in vivo. These reveal an inhibitory role for PROS1 on BM-derived LCs. Collectively, this study highlights a cell-specific regulation of LC differentiation and homeostasis by TAM signaling.

Oral fibroblasts modulate the macrophage response to bacterial challenge.

Tissue damage in chronic periodontal disease is driven by the host response to a dysbiotic microbiota, and not by bacteria directly. Among chronic inflammatory diseases of the oral cavity, inflammation and tissue damage around dental implants (peri-implantitis) is emerging as a major clinical challenge, since it is more severe and less responsive to treatment compared to inflammation around natural teeth. We tested whether oral fibroblasts from the periodontal ligament (PDLF), which are present around natural teeth but not around dental implants, actively regulate inflammatory responses to bacterial stimulation. We show that human PDLF down-regulate TNF-α post-transcriptionally in macrophages stimulated with the oral pathogen Porphyromonas gingivalis. Cell contact and secretion of IL-6 and IL-10 contribute to the modulation of inflammatory cytokine production. Although fibroblasts decreased TNF-α secretion, they enhanced the ability of macrophages to phagocytose bacteria. Surprisingly, donor matched oral fibroblasts from gingival tissues, or fibroblasts from peri-implant inflamed tissues were at least as active as PDLF in regulating macrophage responses to bacteria. In addition, priming fibroblasts with inflammatory mediators enhanced PDLF regulatory activity. A further understanding of the spectrum of fibroblast activities in inflammatory lesions is important in order to design ways to control inflammatory tissue damage.

Oral infection with Porphyromonas gingivalis induces peri-implantitis in a murine model: Evaluation of bone loss and the local inflammatory response.

AIM: Peri-implantitis is a major health concern, with unclear pathogenesis, and with no accessible animal models. Our aim was to establish a mouse model for peri-implantitis and to investigate mediators of inflammation. MATERIALS AND METHODS: Mice were divided into implanted versus non-implanted groups. Implants were inserted immediately following the extraction of the upper first molar. Four weeks following implantation, implanted and non-implanted mice were challenged with either Porphyromonas gingivalis or vehicle (eight mice in each subgroup, 32 mice in total). Alveolar bone loss and expression of inflammatory mediators in the soft tissue were assessed 42 days following infection. RESULTS: Porphyromonas gingivalis infection induced greater bone loss around implants than around teeth. In non-infected animals, the presence of the implant correlated with elevated expression of Il-10, Foxp3 and Rankl/Opg ratio, while Tnf-α levels were decreased relative to tissue around teeth. Six weeks following infection, Tnf-α increased significantly while the expression of Foxp3 decreased in the tissue around the implants. No significant differences in anti- or pro-inflammatory mediators were found around teeth of infected, relative to non-infected mice. CONCLUSIONS: Oral infection with P. gingivalis of mice with implants induced bone loss and a shift in gingival cytokine expression. This mouse model enables exploration of the pathogenesis of peri-implantitis and testing of novel treatments.

GAS6 is a key homeostatic immunological regulator of host-commensal interactions in the oral mucosa.

The oral epithelium contributes to innate immunity and oral mucosal homeostasis, which is critical for preventing local inflammation and the associated adverse systemic conditions. Nevertheless, the mechanisms by which the oral epithelium maintains homeostasis are poorly understood. Here, we studied the role of growth arrest specific 6 (GAS6), a ligand of the TYRO3-AXL-MERTK (TAM) receptor family, in regulating oral mucosal homeostasis. Expression of GAS6 was restricted to the outer layers of the oral epithelium. In contrast to protein S, the other TAM ligand, which was constitutively expressed postnatally, expression of GAS6 initiated only 3-4 wk after birth. Further analysis revealed that GAS6 expression was induced by the oral microbiota in a myeloid differentiation primary response gene 88 (MyD88)-dependent fashion. Mice lacking GAS6 presented higher levels of inflammatory cytokines, elevated frequencies of neutrophils, and up-regulated activity of enzymes, generating reactive nitrogen species. We also found an imbalance in Th17/Treg ratio known to control tissue homeostasis, as Gas6-deficient dendritic cells preferentially secreted IL-6 and induced Th17 cells. As a result of this immunological shift, a significant microbial dysbiosis was observed in Gas6-/- mice, because anaerobic bacteria largely expanded by using inflammatory byproducts for anaerobic respiration. Using chimeric mice, we found a critical role for GAS6 in epithelial cells in maintaining oral homeostasis, whereas its absence in hematopoietic cells synergized the level of dysbiosis. We thus propose GAS6 as a key immunological regulator of host-commensal interactions in the oral epithelium.

CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection-Driven Bone Resorption.

Porphyromonas gingivalis,an anaerobic bacterium strongly linked to infection-driven inflammatory bone erosion, thrives within a highly inflamed milieu and disseminates to distant sites, such as atherosclerotic plaque. We examined the role of monocyte/macrophages in determining the outcome of infection with P. gingivalis. Surprisingly, transient monocyte/macrophage depletion led to greatly improved clearance of P. gingivalis. The chemokine receptors CCR2 and CX3CR1 play a major role in monocyte recruitment and differentiation to Ly6C(hi) vs CX3CR1(hi) subsets, respectively. To determine the contribution of particular monocyte/macrophage subsets to bacterial survival, we challenged chemokine receptor knockout mice and found that P. gingivalis clearance is significantly improved in the absence of CX3CR1. CX3CR1(hi) monocyte/macrophages promote P. gingivalis survival by downregulating neutrophil phagocytosis. Furthermore, CX3CR1 knockout mice resist bone resorption in the oral cavity following challenge with P. gingivalis Our findings provide an explanation for bacterial coexistence alongside an activate neutrophil infiltrate.

Nonsurgical treatment of recurrent gingival pyogenic granuloma: A case report.

Gingival pyogenic granuloma is a relatively common benign form of mucocutaneous lesion. Although surgical excision is considered to be the standard care, several reports have demonstrated a high recurrence rate of the lesion. In this case report a nonsurgical protocol to treat recurring gingival pyogenic granuloma and prevent further recurrence is suggested. The protocol includes strict oral hygiene instructions, scaling, root planing, and maintenance treatment. To the best of our knowledge, this is the first report of conservative nonsurgical management of recurrent gingival pyogenic granuloma lesions.

Porphyromonas gingivalis gingipains selectively reduce CD14 expression, leading to macrophage hyporesponsiveness to bacterial infection.

Cysteine proteases (gingipains) from Porphyromonas gingivalis are key virulence factors in chronic periodontitis. Innate immune receptors CD14, Toll-like receptor (TLR) 2 and TLR4 are important in P. gingivalis recognition. We examined the ability of gingipains to cleave CD14, TLR2 and TLR4, and the consequences for the cellular response to bacterial challenge. Macrophages were exposed to Arg (RgpA and RgpB)- and Lys (Kgp)-gingipains, and residual expression of TLR2, TLR4 and CD14 was determined by flow cytometry. The cellular response to live bacteria following exposure to purified gingipains was evaluated by TNFα production and bacterial phagocytosis. RgpA and Kgp decreased CD14 detection in a concentration (p = 0.0000002)- and time (p = 0.03)-dependent manner, whereas RgpB had no significant effect. TLR2 and TLR4 expression were unaffected. Reduction in CD14 expression was more efficient with Lys-gingipain than with Arg-gingipain. A reduced CD14 surface level correlated with decreased TNFα secretion and bacterial phagocytosis following challenge with live P. gingivalis, but the response to heat-killed bacteria was unaffected. Therefore, gingipains reduce CD14 expression without affecting expression of the bacterial-sensing TLRs. Reduced CD14 expression depends on the gingipain hemagglutinin/adhesion site and results in macrophage hyporesponsiveness to bacterial challenge. Further studies are needed to determine if reduced CD14 expression is linked to periodontitis induced by P. gingivalis.

The role of RgpA in the pathogenicity of Porphyromonas gingivalis in the murine periodontitis model.

AIM: To investigate the in vivo role of gingipains in Porphyromonas gingivalis' virulence, and suggest a possible host mechanisms through which the bacteria cause alveolar bone loss. MATERIALS AND METHODS: Mice were orally infected with P. gingivalis wild type, or the gingipains mutants (RgpA⁻, Kgp⁻, RgpA⁻/Kgp⁻). Mice were analysed for alveolar bone loss using micro-computed tomography. The molecular effects of the proteases were evaluated using the subcutaneous chamber model. Mice were infected with P. gingivalis wild type or mutants. Exudates were analysed for cytokine and leukocytes levels, in vivo phagocytosis, P. gingivalis survival and serum anti-P. gingivalis IgG titres. RESULTS: Only RgpA-expressing bacteria induced significantly alveolar bone loss, and suppressed phagocytosis resulting in increased survival of P. gingivalis in the chamber exudates. In addition, RgpA-expressing bacteria induced higher levels of leukocytes and cytokines 2 h post-infection, and reduced levels of serum anti-P. gingivalis IgG titres 7 days post-infection. CONCLUSIONS: Our findings showed that elimination of RgpA from P. gingivalis diminished inflammation, but augmented phagocytosis and antibody titres, coincidental with reduced alveolar bone loss. These findings support the hypothesis that RgpA is a critical virulence factor in the pathogenesis of experimental periodontitis in mice.

Langerhans cells down-regulate inflammation-driven alveolar bone loss.

Excessive bone resorption is frequently associated with chronic infections and inflammatory diseases. Whereas T cells were demonstrated to facilitate osteoclastogenesis in such diseases, the role of dendritic cells, the most potent activators of naive T cells, remains unclear. Using a model involving inflammation-driven alveolar bone loss attributable to infection, we showed that in vivo ablation of Langerhans cells (LCs) resulted in enhanced bone loss. An increased infiltration of B and T lymphocytes into the tissue surrounding the bone was observed in LC-ablated mice, including receptor activator of NF-κB ligand (RANKL)-expressing CD4(+) T cells with known capabilities of altering bone homeostasis. In addition, the absence of LCs significantly reduced the numbers of CD4(+)Foxp3(+) T-regulatory cells in the tissue. Further investigation revealed that LCs were not directly involved in presenting antigens to T cells. Nevertheless, despite their low numbers in the tissue, the absence of LCs resulted in an elevated activation of CD4(+) but not CD8(+) T cells. This activation involved elevated production of IFN-γ but not IL-17 or IL-10 cytokines. Our data, thus, reveal a protective immunoregulatory role for LCs in inflammation-induced alveolar bone resorption, by inhibiting IFN-γ secretion and excessive activation of RANKL(+)CD4(+) T cells with a capability of promoting osteoclastogenesis.

Direct recognition of Fusobacterium nucleatum by the NK cell natural cytotoxicity receptor NKp46 aggravates periodontal disease.

Periodontitis is a common human chronic inflammatory disease that results in the destruction of the tooth attachment apparatus and tooth loss. Although infections with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are essential for inducing periodontitis, the nature and magnitude of the disease is determined by the host's immune response. Here, we investigate the role played by the NK killer receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an oral infection periodontitis model we demonstrate that following F. nucleatum infection no alveolar bone loss is observed in mice deficient for NCR1 expression, whereas around 20% bone loss is observed in wild type mice and in mice infected with P. gingivalis. By using subcutaneous chambers inoculated with F. nucleatum we demonstrate that immune cells, including NK cells, rapidly accumulate in the chambers and that this leads to a fast and transient, NCR1-dependant TNF-α secretion. We further show that both the mouse NCR1 and the human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in vitro that the interaction of NK cells with F. nucleatum leads to an NCR1-dependent secretion of TNF-α. Thus, the present study provides the first evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that this interaction influences the outcome of F. nucleatum-mediated periodontitis.

Dendritic cells in distinct oral mucosal tissues engage different mechanisms to prime CD8+ T cells.

Although oral dendritic cells (DCs) were shown to induce cell-mediated immunity, the identity and function of the various oral DC subsets involved in this process is unclear. In this study, we examined the mechanisms used by DCs of the buccal mucosa and of the lining mucosa to elicit immunity. After plasmid DNA immunization, buccally immunized mice generated robust local and systemic CD8(+) T cell responses, whereas lower responses were seen by lining immunization. A delayed Ag presentation was monitored in vivo in both groups; yet, a more efficient presentation was mediated by buccal-derived DCs. Restricting transgene expression to CD11c(+) cells resulted in diminished CD8(+) T cell responses in both oral tissues, suggesting that immune induction is mediated mainly by cross-presentation. We then identified, in addition to the previously characterized Langerhans cells (LCs) and interstitial dendritic cells (iDCs), a third DC subset expressing the CD103(+) molecule, which represents an uncharacterized subset of oral iDCs expressing the langerin receptor (Ln(+)iDCs). Using Langerin-DTR mice, we demonstrated that whereas LCs and Ln(+)iDCs were dispensable for T cell induction in lining-immunized mice, LCs were essential for optimal CD8(+) T cell priming in the buccal mucosa. Buccal LCs, however, failed to directly present Ag to CD8(+) T cells, an activity that was mediated by buccal iDCs and Ln(+)iDCs. Taken together, our findings suggest that the mechanisms engaged by oral DCs to prime T cells vary between oral mucosal tissues, thus emphasizing the complexity of the oral immune network. Furthermore, we found a novel regulatory role for buccal LCs in potentiating CD8(+) T cell responses.

Vaccination of mice with Porphyromonas gingivalis or Fusobacterium nucleatum modulates the inflammatory response, but fails to prevent experimental periodontitis.

AIM: To assess the potential of using vaccination with Porphyromonas gingivalis or Fusobacterium nucleatum, in modulating local subcutaneous inflammatory response and alveolar bone loss following coinfection with both bacteria. MATERIALS AND METHODS: Mice were immunized against either P. gingivalis or F. nucleatum. The cytokine response to mixed infection with P. gingivalis and F. nucleatum was evaluated using the subcutaneous chamber model. The alveolar bone loss induced by oral mixed infection was evaluated by micro-CT using the experimental periodontitis model. Serum levels of specific antibodies were determined by ELISA. RESULTS: Vaccination with either bacterium produced a specific humoral response before infection. Animals immunized against either bacteria following a mixed infection with P. gingivalis and F. nucleatum, showed decreased TNFalpha (but not IL-1beta) levels as compared with non-immunized animals. However, the vaccination did not change the level of mixed infection-induced alveolar bone loss when compared with non-immunized animals. Six weeks following the oral mixed infection, specific antibody titres remained high. Furthermore, specific antibodies against the non-immunized bacterium were present at high levels. CONCLUSIONS: While vaccination produced specific antibodies and suppressed the inflammatory response, it failed to prevent or reduce the progression of experimental periodontitis induced by mixed infection with P. gingivalis and F. nucleatum.

Mouse model of experimental periodontitis induced by Porphyromonas gingivalis/Fusobacterium nucleatum infection: bone loss and host response.

AIM: To compare the effect of oral infection with Porphyromonas gingivalis or Fusobacterium nucleatum versus infection with both bacteria on mouse periodontal tissues, and to characterize the inflammatory response. MATERIALS AND METHODS: Mice were orally infected with P. gingivalis, F. nucleatum or both. At 42 days post-infection, alveolar bone loss was quantified using micro-computerized tomography. Tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta levels induced by the infection were quantified using the subcutaneous chamber model. RESULTS: Mice orally infected with F. nucleatum/P. gingivalis exhibited significantly more bone loss compared with that of mono-infected and sham-infected mice. F. nucleatum/P. gingivalis infection also increased the levels of TNF-alpha and IL1beta compared with the levels found in the mono-infected groups. CONCLUSIONS: Polymicrobial infection with P. gingivalis/F. nucleatum aggravates alveolar bone loss and induces a stronger inflammatory response compared with that observed upon infection with either bacterium alone. The results suggest that oral infection of mice with a mixture of P. gingivalis and F. nucleatum may be superior to mono-infection models of experimental periodontitis.

VEGF facilitates periosteal distraction-induced osteogenesis in rabbits: a micro-computerized tomography study.

BACKGROUND AND PURPOSE: Distraction osteogenesis is routinely used for reconstruction of bone. Conversely, it was hypothesized that mechanical traction of the periosteum would induce bone formation, and hence the use of periosteal distraction for induction of osteogenesis has been proposed. Further, it was postulated that intracallus administration of vascular endothelial growth factor (VEGF) would facilitate osteogenesis. To investigate this hypothesis, formation of newly synthesized bone was evaluated using micro-computerized tomography (microCT) and histomorphometry. MATERIALS AND METHODS: Periosteal distractors were placed subperiosteally in one side of the mandible of rabbits, whereas the contralateral served as control. One group of animals received VEGF into the forming callus. Formation of bone was measured using microCT and histological analysis. RESULTS: The results demonstrate formation of new bone following periosteal distraction. Addition of VEGF to the distraction site increased bone synthesis. CONCLUSIONS: microCT and histological analysis validate the hypothesis that mechanical distraction of the periosteum induces osteogenesis and that VEGF has a positive effect on osteogenesis. Periosteal distraction is emerging as a reliable technique for bone regeneration.