Parathyroid hormone administration may modulate periodontal tissue levels of interleukin-6, matrix metalloproteinase-2 and matrix metalloproteinase-9 in experimental periodontitis.

BACKGROUND AND OBJECTIVE: Intermittent administration of the parathyroid hormone (1-34) has an anabolic effect on bone and it has been shown to reduce alveolar bone loss in experimental periodontitis models. The aim of the present study was to investigate the effect of parathyroid hormone on tissue degradation-related factors in an experimental periodontitis model in rats. MATERIAL AND METHODS: Periodontitis was induced in seventy-six male Wistar rats using ligature around the lower right first molars. The animals were then treated with parathyroid hormone (1-34) (T-group) or vehicle (C-group), three times a week for 15 d (C15, T15) or 30 d (C30, T30). At each experimental time-point, the 19 rats were killed in each group and the gingival tissue around the first lower molar was removed and prepared for the following analyses: mRNA expression of interleukin-1 beta, interleukin-6, matrix metalloproteinase (MMP)-2 and MMP-9, and gelatinolytic activity of MMP-2 and MMP-9. Hemimandibles were decalcified, and serial sections were processed and analyzed for interleukin-6 immohistochemistry. Samples were also histochemically stained by tartrate-resistant acid phosphatase (TRAP) to evaluate the number of osteoclasts present. RESULTS: Parathyroid hormone-treated samples showed decreased of levels of mRNA for interleukin-6 in the T30 group (p < 0.01) and of MMP-2 in the T15 and T30 groups (p < 0.05). Zymography assays demonstrated that treatment with parathyroid hormone led to a decrease in MMP-9 activity (p < 0.01). TRAP staining of alveolar bone revealed that osteoclasts were present in higher numbers (p < 0.05) in the groups not treated with parathyroid hormone. CONCLUSION: These data suggest that intermittent administration of parathyroid hormone can down-regulate the expression of biomarkers responsible for connective tissue breakdown and bone resorption, and potentially affect alveolar bone resorption activity.

Analysis of the MMP-9 (C-1562 T) and TIMP-2 (G-418C) gene promoter polymorphisms in patients with chronic periodontitis.

BACKGROUND: Matrix metalloproteinases (MMP)-9 is an important member of the matrix metalloproteinase family. A functional polymorphism has been described in the promoter region of the human MMP-9 gene. A C-to-T base exchange at -1562 creates two different alleles, and the C/T and T/T genotypes promote high activity of the MMP-9 gene promoter, increasing the risk for inflammatory diseases. The metalloproteinase-2 tissue inhibitor (TIMP-2) regulates the activity of MMPs in the extracellular matrix, and a polymorphism at the -418 position of the TIMP-2 gene promoter has been found in a Sp-1 binding site. In this study we have investigated the association between the above-mentioned polymorphisms and chronic periodontitis severity. METHODS: Genomic DNA from oral mucosa of 100 subjects was amplified by polymerase chain reaction and analysed by restriction endonuclease digestion. The significance of the differences in observed frequencies of polymorphisms in moderate and severe disease and healthy groups was assessed by chi(2) test (p<0.05). RESULTS: No association was observed between the polymorphism in the promoter region of MMP-9 (p=0.6693) and chronic periodontitis. The analysis of TIMP-2 showed that the G/G genotype was found at a frequency of 99%. CONCLUSION: The results show that the polymorphism in the promoter region of MMP-9 gene is not associated with chronic periodontitis. The high frequency of GG genotype in the TIMP-2 gene promoter in the population studied did not allow any conclusion regarding its effect on chronic periodontitis.

Cementoblast gene expression is regulated by Porphyromonas gingivalis lipopolysaccharide partially via toll-like receptor-4/MD-2.

Lipopolysaccharides are potent inflammatory mediators considered to contribute to destruction of periodontal tissues. Here, we hypothesized that Porphyromonas gingivalis lipopolysaccharide (P-LPS) treatment would regulate gene expression in murine cementoblasts through Toll-like receptor 4. Real-time (RT)-PCR and Northern blot analysis indicated that P-LPS decreased expression of transcripts for osteocalcin (OCN) and receptor activator of nuclear factor kappaB ligand (RANKL). In contrast, a dose-dependent up-regulation in mRNA levels for osteopontin (OPN) and osteoprotegerin (OPG) was observed. Similarly, ELISA demonstrated decreased RANKL and increased OPG levels. A monoclonal antibody specific for mouse TLR-4/MD-2 partially neutralized the P-LPS effect on cementoblasts. These results indicate that exposure of cementoblasts to P-LPS can alter cell function by regulating markers of osteoclastic activity (e.g., RANKL/OPG), thereby potentially affecting the inflammation-associated resorption of mineralized tissues.

Parathyroid hormone protects against periodontitis-associated bone loss.

Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In addition to the well-established catabolic effects (activation of bone resorption) of PTH, it is now recognized that intermittent PTH administration has anabolic effects (promotion of bone formation). The aim of this study was to investigate whether intermittent administration of PTH in rodents would block the alveolar bone loss observed in rats when a ligature model of periodontitis is used. Morphometric analysis showed that intermittent PTH administration (40 microg/kg) was able to protect the tooth site from periodontitis-induced bone resorption. In addition, there was a significant reduction in the number of inflammatory cells at the marginal gingival area in sections obtained from animals receiving PTH compared with control animals. These findings demonstrated that intermittent PTH administration was able to protect against periodontitis-associated bone loss in a rodent model.

Ultrastructural aspects of connective tissue in hereditary gingival fibromatosis.

OBJECTIVE: The purpose of this study was to analyze the ultrastructure of gingival connective tissue from patients in one family affected by hereditary gingival fibromatosis (HGF). STUDY DESIGN: Electron microscopic examination was performed with gingival tissue from 10 patients from a Brazilian family with 132 members. Fifty of 96 persons at risk for this disorder were affected, which is consistent with an autosomal dominant pattern of inheritance. RESULTS: The extracellular matrix showed flocculent material and collagen fibrils with structural abnormalities and variation in diameter. Increased numbers of oxytalan fibers were identified; however, elastic fibers were rare in the analyzed areas. CONCLUSIONS: The structural alterations found in HGF appear similar to those described in certain other heritable collagen disorders, suggesting that HGF should be included in the group of hereditary diseases in which connective tissue alterations have a distinct pattern, in contrast to reactive fibrotic gingival enlargements with no genetic component.

Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo study.

The present study investigated the effect of nicotine administration on periodontal breakdown resulting from ligature-induced periodontitis in rats. Twenty adult male Wistar rats were used. After anesthesia, a mandibular first molar was randomly assigned to receive a cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments. of daily intraperitoneal injections: A - saline solution, B -0.37 mg of nicotine kg, C -0.57 mg of nicotine kg and D -0.73 mg of nicotine/kg. Thirty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Statistical analysis (ANOVA) revealed greater bone loss (p<0.05) in the ligated teeth of animals which received nicotine (groups B/C D) than in the ligated teeth of animals which received saline solution (group A). In addition, a dose-dependent response was observed among the nicotine groups. A negative effect of nicotine was observed in the unligated teeth of the experimental groups (p<0.05). Therefore, daily administration of nicotine enhanced, in a dose-dependent manner, the effects of local factors in producing periodontal breakdown. Furthermore, the nicotine seemed to have a direct deleterious effect on the periodontal tissues.

The influence of nicotine on the bone loss rate in ligature-induced periodontitis. A histometric study in rats.

BACKGROUND: The present study investigated the possible influence of nicotine on the bone loss rate in the furcation region due to ligature-induced periodontitis in rats. METHODS: Twenty adult male Wistar rats were included. After anesthesia, the tooth was randomly assigned to receive the cotton ligature in the sulcular area, while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments, including daily intraperitoneal injections: group A, 2 microl/g body weight of saline solution; group B, 2 microl/g body weight of a nicotine solution with 0.13 microl of nicotine/ml of saline solution; group C, 2 microl/g body weight of a nicotine solution with 0.19 microl of nicotine/ml of saline solution; and group D, 2 microl/g body weight of a nicotine solution with 0.26 microl of nicotine/ml of saline solution. Thirty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. RESULTS: Intergroup analysis revealed greater bone loss in the ligated teeth of group B (1.01 +/- 0.61 mm2), group C (1.14 +/- 0.72 mm2), and group D (1.36 +/- 0.60 mm2) when compared with group A (0.64 +/- 0.62 mm2) (P <0.01). However, no statistically significant differences in bone loss were found among groups B, C, and D. In addition, no bone loss was observed for unligated teeth (P>0.01). CONCLUSIONS: Within the limits of the present study, nicotine enhanced the effects of the local components of periodontal disease in a non-dose-dependent way; nevertheless, the administration of nicotine did not produce periodontal bone loss by itself.