Local delivery of a CXCR3 antagonist decreases the progression of bone resorption induced by LPS injection in a murine model.

OBJECTIVES: This experimental study was carried out to investigate the effects of locally delivered nanoparticles (AMG-487 NP) containing a CXCR3 antagonist in inhibiting the progression of LPS-induced inflammation, osteoclastic activity, and bone resorption on a murine model. MATERIALS AND METHODS: Thirty, 7-week-old C57BL/6 J male mice were used. Inflammatory bone loss was induced by Porphyromonas gingivalis-lipopolysaccharide (P.g.-LPS) injections between the first and second maxillary molars, bilaterally, twice a week for 6 weeks (n = 20). AMG-487 NP were incorporated into a liposome carrier and locally delivered on sites where P.g.-LPS was injected. Control mice (n = 10) were injected with vehicle only. Experimental groups included (1) control, (2) LPS, and (3) LPS + NP. At the end of 1 and 6 weeks, mice were euthanized, maxillae harvested, fixed, and stored for further analysis. RESULTS: Volumetric bone loss analysis revealed, at 1 week, an increase in bone loss in the LPS group (47.9%) compared to control (27.4%) and LPS + NP (27.8%) groups. H&E staining demonstrated reduced inflammatory infiltrate in the LPS + NP group compared to LPS group. At 6 weeks, volumetric bone loss increased in all groups; however, treatment with the CXCR3 antagonist (LPS + NP) significantly reduced bone loss compared to the LPS group. CXCR3 antagonist treatment significantly reduced osteoclast numbers when compared to LPS group at 1 and 6 weeks. CONCLUSIONS: This study showed that local delivery of a CXCR antagonist, via nanoparticles, in a bone resorption model, induced by LPS injection, was effective in reducing inflammation, osteoclast numbers, and bone loss. CLINICAL RELEVANCE: CXCR3 blockade can be regarded as a novel target for therapeutic intervention of bone loss. It can be a safe and convenient method for periodontitis treatment or prevention applicable in clinical practice.

Buccal bone thickness of maxillary anterior teeth: A systematic review and meta-analysis.

AIM: To systematically review buccal bone thickness (BBT) in the anterior maxilla in different teeth, age groups and genders. MATERIALS AND METHODS: PubMed, EMBASE and Cochrane databases were searched up to April 2020. Clinical and radiographic studies reporting on BBT of maxillary anterior teeth, with at least 10 patients, were included. A meta-analysis was performed using random effect models to report differences of BBT. RESULTS: 50 studies were included. Using bone crest (BC) as a reference point, no significant differences were found in BBT between different tooth types, except for 0.16 mm (95%-CI: 0.02-0.30) increased mid-root thickness of premolars compared to canines. Using the CEJ as a reference point, canines presented with a significantly increased thickness of 0.32 mm (95%-CI: 0.11-0.54) coronally compared to laterals. When BC was used as reference, males demonstrated a significantly increased thickness of 0.21 mm (95%-CI: 0.15-0.27) apically, while middle-aged adults showed a 0.06 mm (95%-CI: -0.12, -0.01) statistically significant increase in the coronal level compared to older adults. CONCLUSIONS: Few maxillary anterior teeth have BBT greater than 1 mm. Buccal bone tends to get thicker from a coronal to apical position along the root surface and from an anterior to posterior position in the arch.

Bacterial infection increases periodontal bone loss in diabetic rats through enhanced apoptosis.

Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α-expressing cells and increased apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3-dependent mechanism.

Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3-dependent mechanism in experimental periodontitis.

The purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced by Aggregatibacter actinomycetemcomitans infection. Thirty-eight diabetic and 33 normal rats were inoculated with A. actinomycetemcomitans and euthanized at baseline and at 4, 5, and 6 weeks after inoculation. Bone loss and the infiltration of polymorphonuclear leukocytes (PMNs) in gingival epithelium were measured in hematoxylin-eosin-stained sections. The induction of tumor necrosis factor alpha (TNF-α) was evaluated by immunohistochemistry and of apoptotic cells by a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay. After A. actinomycetemcomitans infection, the bone loss in diabetic rats was 1.7-fold and the PMN infiltration 1.6-fold higher than in normoglycemic rats (P < 0.05). The induction of TNF-α was 1.5-fold higher and of apoptotic cells was up to 3-fold higher in diabetic versus normoglycemic rats (P < 0.05). Treatment with a caspase-3 inhibitor significantly blocked noninflammatory cell apoptosis induced by A. actinomycetemcomitans infection in gingival epithelium and connective tissue (P < 0.05). These results provide new insight into how diabetes aggravates A. actinomycetemcomitans-induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection.

Association of hyaluronic acid with a collagen scaffold may improve bone healing in critical-size bone defects.

OBJECTIVES: To evaluate the effects of a 1% hyaluronic acid (HA) gel in combination with an absorbable collagen sponge (ACS) in the healing of critical-size calvaria defects in rats. MATERIAL AND METHODS: Thirty-two adult Wistar rats were used. Two 5-mm-diameter critical-size defects were created and the treatments were randomly distributed as follows: (1) 1% HA; (2) 1% HA gel-soaked ACS; (3) control (blood clot); and (4) ACS. The animals were sacrificed 60 days post-surgery, when biopsies were collected and processed for histology and histometric analysis. Bone fill was measured as the difference between the initial and the final defect sizes. Non-parametric tests were used to analyze differences between treatments (α=1%) and a t-test for body weight gain in each treatment group (α=5%). RESULTS: Histological analysis showed bone formation on the edges of the defects, although very limited, and a thin layer of connective tissue occupying the midportion of the defects in the control and the ACS groups. Defects filled with a 1% HA gel and 1% HA gel+ACS had a thicker layer of connective tissue and more new bone formed in the margins of the defects. Linear histometric measures showed no significant differences in the initial defect sizes between the groups (P>0.05). The association 1% HA gel+ACS (0.96 ± 0.14 mm) had significantly greater bone fill than the control (0.5 ± 0.02 mm) and ACS (0.56 ± 0.05 mm)-treated groups (P=0.0043 and 0.0173, respectively). Treatment with a 1% HA gel (0.7 ± 0.14 mm) showed no significant differences when compared with the other treatments. CONCLUSION: Within the limits of this study, a 1% HA gel associated with a collagen scaffold can improve new bone formation in critical-size defects. However, this treatment never resulted in complete closure of the defects and healing in the major portion of the defects was characterized by fibrous tissue.