Reduction Of Alveolar Bone Loss Research Articles

Biomechanical behavior of three‐dimensional bioactive composite constructs on extraction socket remodeling

AbstractObjectivesLoss of mechanostimulation leads to dimensional alterations in the extraction socket. The study aims to use three‐dimensional spatial stimulation of the socket wall to assess if bioactive composite constructs could generate mechanostimulative activity.MethodsAnalysis of the biomechanical behavior of the three‐dimensional bioactive composite constructs was done in a model created using ANSYS, and mechanical properties were assessed using finite element analysis.ResultsTotal deformation on the mandible was higher in alginate bioglass and chitosan alginate bioglass than gelatin. Bioglass composites were capable of generating a higher strain on the surrounding alveolar bone than gelatin. The maximum principal elastic strain and equivalent (von Mises) stress of chitosan and bioglass were higher than those of gelatin.SignificanceDifferential stress/strain generated on the alveolar bone with a three‐dimensional approach from early stages of remodeling will have a profound effect on the reduction of alveolar bone loss.

Milk Kefir therapy reduces inflammation and alveolar bone loss on periodontitis in rats

Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues. This study evaluated the anti-inflammatory and antiresorptive effects of milk kefir (MK) on periodontitis in rats. Micro-Raman spectroscopy was performed on MK at different fermentation times to verify the presence of Lactobacillus kefiri. From these results, Wistar rats were divided into the following groups: C (Control); EP (experimental periodontitis); K1 (animals that received MK with one day of fermentation); K1+EP; K4 (animals without EP using MK with four days of fermentation) and K4+EP. MK was administered 28 days before EP induction and during the disease development period (11 days). On day 28, in the EP groups, periodontitis was induced. The animals were euthanized on day 39. The hemimaxillae were removed and the following parameters were evaluated: micro-Raman analysis of the presence of inflammation; histomorphometric analysis to quantify alveolar bone loss and immunohistochemistry for IL-6, TNF-α, IL-Iβ and IL-10 in the periodontal ligament. Micro-Raman analysis showed that four days fermentation MK has a higher intensity spectrum of L. kefiri. Furthermore, the administration of this probiotic reduced the intensity of the inflammation spectrum when compared to one day fermentation MK. It was observed that the animals from the K4+EP group showed significant reduction of alveolar bone loss, as well as a lower IL-6, TNF-α and IL-Iβ immunoexpression and a higher IL-10 immunoexpression, when compared to EP groups. We conclude that MK has anti-inflammatory and antiresorptive effects on periodontitis in rats and that these effects are fermentation time dependent.

Influence of antimicrobial photodynamic therapy as an adjunctive to scaling and root planing on alveolar bone loss: A systematic review and meta-analysis of animal studies.

The study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) as adjunctive therapy to scaling and root planing in experimental periodontitis in rats, with or without systemic involvement, by means of histometric analysis of the furcation region. Systematic search was done using PubMed/MEDLINE, SCOPUS, EMBASE and ProQuest databases. Quantitative analysis of alveolar bone loss, with subcategories for the experimental periods studied, was performed. The analysis was performed through the mean difference (MD), with 95% confidence intervals (CIs) and according to SYRCLE guidelines. Nine studies were considered eligible. A statistically favorable difference was observed for the use of aPDT in all periods studied in systemically healthy animals at 7 (P < 0.00001; MD: -0.71; 95% CI: [-0.85, -0.58]; I2: 90%), 15 (P < 0.00001; MD: -0.49; 95% CI: [-0.62, -0.37]; I2: 88%), and 30 (P < 0.00001; MD: -0.53; 95% CI: [-0.65, -0.41]; I2: 80%) days postoperatively. The difference was also observed for modified animals at 7 (P < 0.00001; MD: -1.03; 95% CI: [-1.43, -0.62]; I2: 97%), 15 (P < 0.00001; MD: -1.04; 95% CI: [-1.62, -0.46]; I2: 99%), and 30 (P < 0.00001; MD: -0.88; 95% CI: [-1.37, -0.39]; I2: 97%) days postoperatively. The adjunctive use of aPDT favored the reduction of alveolar bone loss in experimental periodontitis in rats, and this result was more evident in systemically compromised rats.

Evaluation of bilateral mandibular distal extension implant supported overdenture retained by two clasp assemblies

Purpose Clinically evaluate the effect of clasp design on tissue health around abutment teeth and implants assisting mandibular bilateral distal extension removable partial overdenture. M&M: 12 partially edentulous patients with mandibular bilateral free end saddle opposed by almost dentulous intact maxilla with the first premolars. Two dental implants were inserted at the first molar areas to support a bilateral distal extension partial overdenture with lingual bar as major connector. According to clasp design patients are divided in two groups. Group I: six patients for whom removable partial overdentures were retained with O-ring attachment to the implants and RPI clasp to the first premolar abutment teeth. Group II: six patients for whom removable partial overdentures were retained with O-ring attachment to the implants and conventional Aker clasp to the abutment teeth. Clinical evaluation Gingival index, probing depth and teeth mobility together with radiographic evaluation for alveolar bone loss around both implants and abutments using Digora for Windows were carried out immediately at insertion, 3, 6, and 9 months after insertion. Results After the first 3 months gingival index and probing depth increased significantly in both groups within the physiological limit while at the end of ninth month after insertion, no statistically significant difference between two groups. Differences between two groups regarding mobility and alveolar bone loss around abutment teeth through all the study periods, there is no statistically significance difference between the two groups. Regarding mobility and alveolar bone loss around implants through all the study periods, there is no statistically significant difference between results. Conclusion Presence of bilateral posterior implants reduce most problems of mandibular Kennedy class I such as preservation of abutment teeth, reduction of alveolar bone loss around the abutments and reduction the problems of rigid (Aker) clasp.

Induction of M2 Macrophages Prevents Bone Loss in Murine Periodontitis Models

Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-α secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro–computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis–induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-Β ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.

Effects of quorum-sensing inhibition on experimental periodontitis induced by mixed infection in mice.

This study aimed to verify, in invivo settings, whether quorum-sensing inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial colonization of periodontal tissues. In BALB/c mice, periodontitis was induced through oral inoculation with P.gingivalis and F.nucleatum six times during a 42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were administered simultaneously with bacterial infection. Linear and volumetric modifications of interproximal alveolar bone levels were compared between groups using micro-computed tomography. Total bacteria, and P.gingivalis and F.nucleatum DNA in periodontal tissues, were quantified using real-time PCR. Radiographic linear measurements demonstrated a significant reduction of alveolar bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors when compared with the co-infection group. This was confirmed by a significant increase of residual bone volume in the test group. While total bacterial genes in the treatment group significantly decreased by 93% in periodontal tissue samples when quorum sensing inhibitors were administered, no significant differences of P.gingivalis DNA were found. Quorum sensing inhibitors reduced periodontal breakdown and bacterial infection in periodontal tissues after co-infection with P.gingivalis and F.nucleatum.

Exenatide and Sitagliptin Decrease Interleukin 1β, Matrix Metalloproteinase 9, and Nitric Oxide Synthase 2 Gene Expression But Does Not Reduce Alveolar Bone Loss in Rats With Periodontitis.

New drugs for the treatment of diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists and inhibitors of dipeptidyl peptidase-4 (DPP-4) have shown pleiotropic effects on bone metabolism and anti-inflammatory properties. The aim of this study is to evaluate the effects of exenatide (GLP-1 agonist) and sitagliptin (DPP-4 inhibitor) during periodontitis induction by ligature insertion in rats. Forty rats were divided into four groups: 1) animals with induced periodontitis that received exenatide (EG); 2) animals with induced periodontitis that received sitagliptin (SG); 3) animals with induced periodontitis and without drug treatment (LG); and 4) animals without induced periodontitis and without drug treatment (controls). The drugs were administered for 28 days. On the day the animals were sacrificed, blood was collected for analysis of glucose and DPP-4 levels. The gene expressions of prostaglandin-endoperoxide synthase 2, tissue inhibitor of metalloproteinase 1, Dpp4, nitric oxide synthase 2 (Nos2), interleukin 1β (Il1b), and matrix metalloproteinase 9 (Mmp9) in the gingiva; support and alveolar bone loss; connective tissue attachment; and the quantity of gingival collagen were evaluated. Exenatide and sitagliptin treatments have led to a lower percentage of weight gain but did not influence glycemia. Sitagliptin reduced the serum concentration of DPP-4. Interestingly, although the gene expression profile has revealed a downregulation of Mmp9, Nos2, and Il1b in both EG and SG compared to LG, a significant protective effect was not observed on alveolar bone and collagen tissue in this model. Regardless of the reduction of the expression of Il1b, Nos2, and Mmp9, the drugs were not effective in the stabilization or reduction of alveolar bone loss and collagen degradation in rats.

Comparative evaluation of the efficacy of the cyclooxygenase pathway inhibitor and nitric oxide synthase inhibitor in the reduction of alveolar bone loss in ligature induced periodontitis in rats: An experimental study.

Background:Alveolar bone loss is the most striking feature of periodontal disease. The aim of this study was to investigate the effect of a cyclooxygenase (COX) pathway inhibitor and nitric oxide synthase (NOS) inhibitor in the reduction of alveolar bone loss in an experimental periodontal disease (EPD) model.Materials and Methods:The study was conducted on 60 Wistar rats divided into three groups of 20 rats each and then subjected to a ligature placement around the left maxillary second molars. Group 1 rats were treated with COX inhibitor (diclofenac sodium 10 mg/kg/d), group 2 with NOS inhibitor (aminoguanidine hydrochloride 10 mg/kg/d) and group 3 served as controls, receiving only saline, intraperitoneally 1h before EPD induction and daily until the sacrifice on the 11th day. Leukogram was performed before ligation, at 6 h and at the first, seventh and 11th days after EPD induction. After sacrifice, all the excised maxillae were subjected to morphometric and histometric analysis to measure the alveolar bone loss. Histopathological analysis was carried out to estimate cell influx, alveolar bone and cementum integrity.Results:Induction of experimental periodontitis in the rat model produced pronounced leucocytosis, which was significantly reduced by the administration of diclofenac sodium and aminoguanidine on the 11th day. In morphometric and histometric examinations, both the test drugs significantly (P < 0.05) inhibited the alveolar bone loss as compared with the control group.Conclusion:Both COX inhibitor and NOS inhibitor are equally effective in inhibiting the inflammatory bone resorption in an experimental periodontitis model.

Sublingual vaccination with outer membrane protein of Porphyromonas gingivalis and Flt3 ligand elicits protective immunity in the oral cavity

In this study, we demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40k-OMP) sublingually administered with a cDNA vector plasmid encoding Flt3 ligand (pFL) elicited a protective immune response. Sublingual immunization of mice with 40k-OMP plus pFL induced significant serum IgG and IgA, as well as salivary IgA, antibody responses that were comparable to those induced by 40k-OMP plus cholera toxin as adjuvant. When the subclasses of 40k-OMP-specific IgG were evaluated, sublingual immunization with 40k-OMP plus pFL induced both IgG1 and IgG2a antibody responses. Sublingual delivery of pFL resulted in FL expression in submandibular glands, but not in other oral tissues. Furthermore, marked increases in FL protein occurred in saliva and serum, and the frequencies of both CD11c +CD11b + and CD11c +CD8α + dendritic cells with up-regulated expression of CD80, CD86 and CD40 molecules significantly increased in submandibular lymph nodes and spleen. Importantly, the mice given sublingual 40k-OMP plus pFL showed a significant reduction of alveolar bone loss caused by oral infection with P. gingivalis. These findings suggest that sublingual administration of 40k-OMP with pFL acts as an effective and safe mucosal vaccine against oral P. gingivalis infection, and may be a useful tool in the prevention of chronic periodontitis.

Immunogenicity and Protective Efficacy of Heat-Killed Recombinant Lactobacillus casei Expressing Outer Membrane Protein of Porphyromonas gingivalis

This study seeks to access the potential of a heat-killed recombinant Lactobacillus casei expressing 40-kDa outer membrane protein of Porphyromonas gingivalis (L. casei/40k-OMP) as a nasal vaccine against P. gingivalis infection. The 40-kDa outer membrane protein of P. gingivalis (40k-OMP) were expressed on the surface of L. casei using poly-γ-glutamate symthetase A (pgsA). Nasal immunization with heat-killed L. casei/40k-OMP induced significant 40k-OMP-specific serum IgG, IgA and saliva IgA antibody responses. Antibody-forming cell analysis revealed high numbers of 40k-OMP-specific IgA antibody-forming cells in the submandibular glands of mice given heat-killed L. casei/40k-OMP. Importantly, nasal administration of heat-killed L. casei/40k-OMP resulted in the significant reduction of alveolar bone loss caused by oral infection with P. gingivalis. Because L. casei is one of major probiotic bacterias, nasal administration of heat-killed L. casei/40k-OMP should be an effective and safe mucosal vaccine for humans against P. gingivalis infection and may be an important tool for prevention of chronic periodontitis.

Transcutaneous Immunization with the Outer Membrane Protein of P. gingivalis Elicits Long-term Protective Immunity in the Oral Cavity

A previous study showed that transcutaneous immunization with the 40-kDa outer membrane protein of Porphyromonas gingivalis (40k-OMP) elicits humoral immunity that protects from abscess induction by P. gingivalis. In this study, we assessed the potential of 40k-OMP as a transcutaneous vaccine against oral P. gingivalis infection. Transcutaneous immunization of mice with 40k-OMP alone or 40k-OMP plus cholera toxin (CT) elicited 40k-OMP-specific IgG and IgA antibody (Ab) responses in serum and IgG Abs in saliva. These Ab responses were maintained for at least 1 year after immunization, except for serum IgA Abs induced by 40k-OMP alone. Importantly, IgG Abs generated by transcutaneous immunization with 40k-OMP alone, or with 40k-OMP plus CT, inhibited hemagglutinating activity of P. gingivalis. Furthermore, mice transcutaneously immunized with 40k-OMP plus CT, but not 40k-OMP alone, showed significant reduction of alveolar bone loss caused by oral infection with P. gingivalis even 1 year after immunization. These results suggest that 40k-OMP is an effective transcutaneous vaccine against P. gingivalis infection and may be an important tool for the prevention of chronic periodontitis.

Nasal Vaccination with the 40-Kilodalton Outer Membrane Protein ofPorphyromonas gingivalisand a Nontoxic Chimeric Enterotoxin Adjuvant Induces Long-Term Protective Immunity with Reduced Levels of Immunoglobulin E Antibodies

In this study, we demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40-kDa OMP) nasally administered with a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli (mCTA/LTB) elicited a long-term protective immune response. Immunization with the 40-kDa OMP and mCTA/LTB induced high levels of 40-kDa-OMP-specific immunoglobulin G (IgG) and IgA antibodies (Abs) in sera and elicited a significant IgA anti-40-kDa OMP Ab response in saliva. These Ab responses were maintained for at least 1 year after the immunization. Although using adjuvant mCTA/LTB gave Ab responses in the saliva comparable to those obtained using native cholera toxin (nCT) as the adjuvant, the levels of total IgE and 40-kDa-OMP-specific IgE Abs as well as interleukin-4 levels induced by the immunization with mCTA/LTB were lower than those induced by the immunization with nCT. Importantly, IgG Abs generated by nasal immunization with the 40-kDa OMP plus mCTA/LTB inhibited the coaggregation and hemagglutinin activities of P. gingivalis. Furthermore, the mice given nasal 40-kDa OMP plus mCTA/LTB showed a significant reduction of alveolar bone loss caused by oral infection with P. gingivalis even 1 year after the immunization compared to the loss in unimmunized mice. Because mCTA/LTB is nontoxic, nasally administered 40-kDa OMP together with mCTA/LTB should be an effective and safe mucosal vaccine against P. gingivalis infection in humans and may be an important tool for the prevention of chronic periodontitis.

Arg-gingipain A DNA Vaccine Prevents Alveolar Bone Loss in Mice

One major pathogenic factor of Porphyromonas gingivalis is Arg-gingipain (Rgp), an arginine-specific cysteine proteinase. To clarify the effect of rgpA DNA vaccine, we immunized BALB/c mice via the abdomen with a Gene Gun or via the nasal cavity weekly for 6 weeks. After immunization, the mice were challenged orally with P. gingivalis. Immunization elicited IgG responses against P. gingivalis in both groups. Nasal immunization also induced sIgA against P. gingivalis, although Gene Gun immunization did not. Reduction of alveolar bone loss was observed in both groups at 42 days following initial infection. This effect was more pronounced in the intranasal immunization group than in the Gene Gun group. The results of this study suggest that immunization with rgpA DNA vaccine via the nasal cavity is an effective method for preventing alveolar bone loss incurred by infection with P. gingivalis.