L Chai

Genetic polymorphism studies in periodontitis and Fcγ receptors

Periodontitis is a complex chronic subgingival plaque-induced inflammatory disease influenced by multiple factors, including genetics, behavior and the environment. Many genetic association studies have been conducted in periodontology. One of the most extensively investigated gene families is the Fcγ receptor gene family, which plays a key role in regulating host immune responses to bacteria. Unlike other genetic polymorphisms reported in periodontology, most Fcγ receptor polymorphisms reported not only have established biological functions but are reported to associate with other autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. There are, however, few recent reviews summarizing the association of this gene family with periodontitis. This article critically reviews the current understanding of genetic polymorphism studies in periodontitis, then summarizes the research status of Fcγ receptor polymorphisms and periodontitis and also of other genes involved in the regulatory network of Fcγ receptors, with special reference to their anticipated biological roles. Moreover, some possible future research directions in the related area are discussed.

Single nucleotide polymorphisms of complement component 5 and periodontitis.

BACKGROUND AND OBJECTIVE Polymorphisms of host defence genes might increase ones risks for periodontitis. This study investigated whether tagging single nucleotide polymorphisms (SNPs) of the gene encoding complement component 5 (C5) are associated with periodontitis in a Hong Kong Chinese population. MATERIAL AND METHODS Eleven tagging SNPs of 229 patients with at least moderate periodontitis and 207 control subjects without periodontitis were genotyped using an i-plexGOLD MassARRAY mass-spectrometry system. RESULTS Genotype AG of SNP rs17611 was more prevalent in the group of periodontitis patients than in the controls (54.6% vs. 41.7%, p = 0.007). The haplotype CGCA of the haplotype block consisting of rs1035029, rs17611, rs25681 and rs992670 was significantly associated with periodontitis in a dominant model (p = 0.001). The SNP rs17611 showed high linkage disequilibrium with rs1035029, rs25681 and rs992670. Smoking was also significantly associated with periodontitis (p = 0.006). CONCLUSION The tagging SNP rs17611 of the C5 gene and smoking may be associated with periodontitis among the Hong Kong Chinese population.

Effects of vascular endothelial growth factor (VEGF) on MC3T3-E1

UNLABELLED Osteogenesis and angiogenesis are closely correlated. Vascular endothelial growth factor (VEGF) is believed to play a critical role in skeletal development. OBJECTIVE To investigate whether VEGF has direct effects on bone cells activities and to better understand how VEGF promotes bone remodeling. MATERIALS AND METHODS MC3T3-E1 cell line was cultured with and without VEGF in vitro. The cells in both control and test groups were collected at different culture time points of 24, 48 and 72 h. Real-time polymerase chain reaction (qPCR) was carried out to quantify the mRNA expression of VEGF receptor (VEGFR2), alkaline phosphatase (ALP) and osteocalcin (OCN), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa β ligand (RANKL). RESULTS The expression of VEGFR2 significantly increased by 53% at 24 h and remained increased by 8% at 72 h compared to control (p < 0.05). ALP showed an early increase by 73% at 24 h (p < 0.001), but dropped by 14 and 41% at 48 and 72 h, respectively (p < 0.05). OCN was down-regulated by 41% at 24 h but then up-regulated by 149% at 72 h (p < 0.001). The expression of OPG significantly decreased by 7% at 24 h (p < 0.001) while dramatically increased by 133% at 72 h (p < 0.001). RANKL remained unchanged at all three time points (p > 0.05). CONCLUSION VEGF promotes bone remodeling by direct effects on osteoblastic cells via regulating gene expression of ALP, OCN, and OPG through VEGFR2 signaling pathway.

SNPs of Fc-gamma Receptor Genes and Chronic Periodontitis

Genetic polymorphisms of host defense genes might increase risk for periodontitis. This case-control study investigated whether 102 single-nucleotide polymorphisms (SNPs) in Fc gamma receptor (FCGR) genes are associated with chronic periodontitis. Cases were 190 Hong Kong Chinese patients with severe chronic periodontitis, and there were 169 periodontitis-free individuals as controls. Genotype CC and allele C of rs445509 (p < 0.0001, OR = 0.30) of FCGR3A were significantly more prevalent among control individuals than among cases, after adjustment for age, sex, and smoking. Smoking was significantly associated with chronic periodontitis (p = 0.003, OR = 3.35). Within the limitations of this study, SNP rs445509 of FCGR3A seem to be negatively associated, while smoking was positively associated, with severe chronic periodontitis among Hong Kong Chinese.

Expression of Survivin and Caspase 3 in Oral Squamous Cell Carcinoma and Peritumoral Tissue

This study was conducted to investigate the expression of survivin and caspase 3 in oral squamous cell carcinoma and peritumoral tissue, and possible pathogenesis mechanisms. We used ELISA and western blotting to detect the protein expression levels of survivin and caspase 3 in tissue. In situ hybridization and real-time PCR were applied to assess mRNA expression levels. In this study, 13 tumor samples and 13 peritumoral tissue samples were collected from oral squamous cell carcinoma patients and 10 normal tissue samples obtained from patients without tumor. The result showed that the protein and mRNA expression of survivin in carcinoma was the highest among three types of tissue; following was that in peritumoral tissue. No difference in caspase 3 zymogen between peritumoral tissue and normal tissue could be found, while it was evidently decreased in carcinoma tissue. Activated caspase 3 was detected in normal tissue but could not be identified in peritumoral or carcinoma tissue. Our results indicate that the expression of survivin is apparently elevated in tumoral and peritumoral tissue. Expression of activated caspase 3 was not detected in tumoral tissue and the expression of caspase 3 zymogen was decreased in tumoral tissue. Our findings suggest that survivin may inhibit both synthesis and activation of caspase 3, hence inhibiting cell apoptosis and facilitating eventual development of oral squamous cell carcinoma.

Effects of medicinal herb salvia miltiorrhiza on osteoblastic cells in vitro

Sufficient osteoinduction is essential for the success and effectiveness of bone grafting. It was previously found that Salvia Miltiorrhiza (SM), a commonly used Chinese herb increased osteogenesis in vivo. The aim of this study is to investigate the effects of SM on bone cells in vitro, in an attempt to get a better understanding on how SM can promote bone remodeling. MC3T3‐E1, an osteoblastic cell line, was cultured with SM for different time intervals (24, 48, and 72 h), whereas the control group consisted of cells cultured without any intervention. The mRNA expression of alkaline phosphatase (ALP), osteocalcin (OCN), osteoprotegerin (OPG), and the receptor activator of nuclear factor kappa B ligand (RANKL) were examined by real‐time polymerase chain reaction (qPCR). The expression of ALP showed an early increase at 24 h by 50% (p < 0.001) and at 48 h by 13% (p < 0.001). OCN was decreased by 22% at 24 h (p < 0.001) but increased by 50% and 88% at 48 and 72 h, respectively (p < 0.001). RANKL showed an early increase at the first two time points of 24 and 48 h by 45% (p < 0.001) and 36% (p < 0.01), respectively, while OPG was up‐regulated at the latter two time points by 10% at 48 h (p < 0.01) and 68% at 72 h (p < 0.001). Thus, OPG/RANKL was down‐regulated first, and then up‐regulated. SM enhances bone remodeling by regulating the gene expression of ALP, OCN, OPG, and RANKL. It is a potential medicinal herb to be utilized in the application that requires stimulation in bone cell activities.

Salvia Miltiorrhiza Induces VEGF Expression and Regulates Expression of VEGF Receptors in Osteoblastic Cells

This study investigated in vitro whether Salvia Miltiorrhiza Bunge (SM) induces vascular endothelial growth factor (VEGF) expression and regulates expression of VEGF receptors 1 (VEGFR‐1) and 2 (VEGFR‐2) on osteoblasts. MC3T3‐E1 cells were cultured with SM and VEGF at points 24, 48 and 72 h. A blank control was included. The mRNA expression of VEGF, VEGFR‐1 and VEGFR‐2 was examined using real‐time polymerase chain reaction. VEGF protein expression was examined using enzyme linked immunosorbent assay. SM increased VEGF mRNA expression by 21% at 24 h (p < 0.05), 5% (p < 0.05) at 48 h and 74% (p < 0.001) at 72 h, while external VEGF intervention decreased the internal VEGF expression by 51% at 24 h (p < 0.001) and increased it by 126% at 72 h (p < 0.001). SM increased VEGF protein at 72 h (p < 0.05). VEGFR‐1 mRNA expression, in response to SM, decreased by 8% (p < 0.05) at 72 h and decreased following VEGF at 24 and 72 h by 20% (p < 0.001) and 15%, respectively, (p < 0.001). VEGFR‐2 mRNA expression increased following SM at 24 and 48 h by 25% (p < 0.05) and 73% (p < 0.05), respectively, and decreased at 72 h by 13% (p < 0.05). It was concluded that SM modulated expression of VEGF and its receptors in MC3T3‐E1 cells. Copyright

Single nucleotide polymorphisms of Fc-gamma receptor genes and periodontitis

Background: The significance of access to dental care on oral conditions in older subjects is limited. We hypothesized that dental care control for aging effects on oral and periodontal conditions. Materials and methods: 1020 randomly selected subjects between age 60 and 96 from the Swedish National Study on Aging and Care Blekinge study received comprehensive medical and dental examinations. Results: Dentate women and men had, on average,18.4 teeth (S.D. ± 7.6), and 18.9 teeth (S.D.±7.5) (P = 0.37) respectively. In the youngest age group with infrequent dental visits 37% had > 20 teeth, and 73% had > 20 teeth if they had annual visits. Among old-old infrequent dental visitors 1.8% had > 20 teeth and 37% had > 20 teeth with annual visits. Across age groups, the overall % bleeding on probing was 23%. When adjusting for age, GLM univariate analysis failed to demonstrate an effect of frequency of dental visits and ABL scores (P = 0.18) but frequent dental visitors had significantly more teeth than infrequent visitors (P = 0.001). Conclusions: Tooth loss and extent of alveolar bone loss increase with age. Frequent dental visits seem to preserve teeth but has no impact on the amounts of deposits, gingival inflammation, or alveolar bone levels.This free journal suppl. entitled: Special Issue: Abstracts of Europerio 6, 4-6 June 2009, Stockholm, SwedenBackground: The periodontal ligament cells (PDL cells) play a key role in the formation of the periodontal ligament but these cells have other functions as well. The PDL cells express estrogen rec ...