VDR deficiency affects alveolar bone and cementum apposition in mice

Objective

To compare the mineralisation density (MD), morphology and histology of alveolar bone and cementum amongst VDR +/+, VDR −/−, and VDR −/− groups supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25% phosphorous.

Methods

Four groups of mice (6 mice/group) were identified by genotyping: VDR +/+ mice (VDR wild type), VDR −/− mice (VDR deficient), VDR −/− offsprings derived from VDR −/− parents receiving a supplemental diet (early rescued), and VDR −/− mice fed with a supplemental diet beginning at age one month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was used to compare MD and morphology of alveolar bone and cementum. H–E and Toluidine blue staining was used to examine the ultrastructure of the alveolar bone and cementum at matched locations.

Results

In VDR −/− group, alveolar bone and cementum failed to mineralise normally. Early rescue increased MD of alveolar bone in VDR −/− mice with excessive alveolar bone formation, but which not observed in late rescue group. MD and morphology of cementum–dentine complex in both early and late rescue groups were comparable with VDR +/+ group when feeding with high-calcium rescue diet.

Conclusions

VDR affects alveolar bone mineralisation and formation systemically and locally. However, cementum apposition and mineralisation is mainly regulated by calcium concentrations in serum.     

Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways

A hallmark of infection with the gram‐negative pathogen Porphyromonas gingivalis is the induction of a chronic inflammatory response. P. gingivalis induces a local chronic inflammatory response that results in oral inflammatory bone destruction, which manifests as periodontal disease. In addition to chronic inflammation at the initial site of infection, mounting evidence has accumulated supporting a role for P. gingivalis‐mediated periodontal disease as a risk factor for several systemic diseases including, diabetes, preterm birth, stroke, and atherosclerotic cardiovascular disease. A growing number of in vitro studies have demonstrated that P. gingivalis infection stimulates cell activation commensurate with expected responses paralleling inflammatory atherosclerotic‐type responses. Furthermore, various mouse models have been used to examine the ability of P. gingivalis to stimulate chronic inflammatory plaque accumulation and recent studies have pointed to a pivotal role for innate immune signaling via the Toll‐like receptors in the chronic inflammation associated with P. gingivalis infection. In this review we discuss the pathogen and host cell specificity of these responses and discuss possible mechanisms by which this oral pathogen can induce and maintain a chronic state of inflammation at sites distant from oral infection.     

Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses

AIM: To investigate in individuals with symptomatic dental abscesses the occurrence of functional polymorphisms within five genes involved with the immune response. The functional gene polymorphisms analysed were CD14 (-260 C/T), IL1B (+3954 C/T), IL6 (-174 G/C,), IL10 (-1082 G/A) and TNFA (-308 G/A). METHODOLOGY: Genomic DNA obtained from oral swabs from individuals with symptomatic dental abscesses and asymptomatic inflammatory periapical lesions, without previous exacerbation, was submitted to restriction fragment length polymorphism (RFLP) analyses to determine each individual genotype. The chi-square and principal components analysis tests were used for statistical analysis. RESULTS: A significant association was observed between the occurrence of the GG genotype or the G allele expression of the polymorphic locus-174 (G/C) of the IL6 gene, and the presence of the symptomatic dental abscesses in women and in individuals < or =35 years old. The principal components analysis suggested predominance of the symptomatic dental abscesses in individuals displaying: high-producer IL6 genotype; intermediate and high-producer IL1B genotypes and low-producer TNFA genotype. CONCLUSIONS: The present study suggests that genetic factors are associated with susceptibility to develop symptomatic dental abscesses.     

Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis

BACKGROUND: Genetic polymorphisms for cytokines and their receptors have been proposed as potential markers for periodontal disease. Tumor necrosis factor receptor 2 (TNFR2) is one of the cell surface receptors for TNF-alpha. Recent studies have suggested that TNFR2 gene polymorphism is involved in autoimmune and other diseases. OBJECTIVES: The aim of the present study is to evaluate whether TNFR2(+587T/G) gene polymorphism is associated with chronic periodontitis (CP). METHODS: One hundred and ninety-six unrelated subjects (age 40-65 years) with different levels of CP were identified according to established criteria, including measurements of probing pocket depth (PPD), clinical attachment level (CAL), and alveolar bone loss (BL). All subjects were of Japanese descent and non-smokers. Single nucleotide polymorphism at position +587(T/G) in the TNFR2 gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. RESULTS: The frequency and the positivity of the +587G allele were significantly higher in severe CP patients than in controls (p=0.0097; odds ratio=2.61, p=0.0075; odds ratio=3.06). In addition, mean values of PPD, CAL, and BL were significantly higher in the +587G allele positive than in the negative subjects (p=0.035, 0.022, and 0.018, respectively). CONCLUSIONS: These findings suggest that the TNFR2(+587G) polymorphic allele could be associated with severe CP in Japanese.     

Possible involvement of extracellular signal-regulated kinases 1/2 in mitogenic response of periodontal ligament cells to enamel matrix derivative

The efficacy of enamel matrix derivative (EMD) as an adjunct to periodontal regenerative therapy has been demonstrated in recent clinical studies, however, little is known about its molecular mechanism (s). We examined the mitogenic response of cultured periodontal ligament (PDL) cells to EMD and characterized associated changes in proliferation-related intracellular signaling molecules, including mitogen-activated protein kinases (MAPK) and Akt kinases/protein kinase B (Akt/PKB) kinases. The DNA synthesis of PDL cells increased following treatment with EMD at concentrations higher than 1 microg ml(-1). This mitogenic response to EMD was associated with the selective activation of extracellular signal-regulated kinase (ERK) 1/2. No other MAPKs, or Akt/PKB kinases, responded to EMD stimulation. The EMD induction of DNA synthesis and activation of ERK 1/2 were diminished by pretreatment with suramin, an inhibitor of receptor tyrosine kinases (RTK). The signaling pathway induced by EMD from RTK to ERK 1/2 was similar to that activated by epidermal growth factor (EGF), although the specific binding of 125I-EGF to PDL cells was not affected by pretreatment or concomitant treatment with EMD. These findings suggest that EMD elicits its mitogenic signal through an EMD-specific RTK towards ERK 1/2.     

头颈部恶性肿瘤患者血清可溶性白介素2受体水平

目的:研究头颈部恶性肿瘤患者血清可溶性白介素2受体(sIL-2R)水平的变化。方法:用双抗体夹心法对60例头颈部恶性肿瘤患者,60例良性肿瘤患者以及50例健康对照者的血清sIL-2R水平进行检测。结果:头颈部恶性肿瘤患者组血清sIL-2R水平显著高于健康对照组(P<0.01),而良性肿瘤患者组血清sIL-2R水平与健康对照组无统计学差异(P>0.05)。结论:血清中高sIL-2R水平可能与头颈部恶性肿瘤的发生有相关性。     

重组人类可溶性受体对大鼠正畸牙移动影响的研究

目的研究局部注射不同浓度重组人类可溶性受体对大鼠正畸牙移动进程的影响，了解其在牙周局部发挥作用的最小有效浓度范围。方法选取52只雄性SD大鼠，随机分为四组，用螺旋拉簧牵引大鼠左上第一磨牙近中移动，实验组第一天起局部分别注射不同浓度的重组人类可溶性IL-1和TNF受体，14天后测量磨牙移动距离，并制作切片进行HE及TRAP染色分析。结果与对照组相比，各受体组浓度为4ug／ml、0．8ug／ml、0．16ug／ml小组磨牙移动距离均大幅度减少（P〈0．01），牙槽骨表面及牙根表面TRAP染色阳性细胞数量也明显减少（P〈0．01），而浓度为0．032ug／ml小组却没有统计学意义（P〉0．05），且各受体组相同浓度小组问差异无统计学意义（P〉0．05）。结论在大鼠正畸牙局部注射重组人类可溶性受体发挥作用的最小有效浓度范围为0．032ug／ml-0．16ug／ml。