Liu Kn

Elevated Plasma Calcifediol Is Associated With Aggressive Periodontitis

BACKGROUND Vitamin D is associated with a number of inflammatory diseases and plays a significant role in regulating bone metabolism. Serum calcifediol was demonstrated to be potentially associated with periodontal disease. The purpose of this study was to evaluate whether an association exists between plasma calcifediol concentrations and aggressive periodontitis (AgP) and whether plasma levels of bone-related biomarkers (osteocalcin, alkaline phosphatase, calcium, and phosphorus) regulated by vitamin D are related to AgP. METHODS Sixty-six patients with generalized AgP, 52 patients with chronic periodontitis, and 60 healthy controls were included in this study. Periodontal examination consisted of probing depth, attachment loss, and bleeding index measurements. Hematic calcifediol and bone-related biomarker levels were detected using radioimmunity assay kits or a biochemical analyzer. RESULTS Plasma calcifediol levels in patients with AgP were higher than those of healthy controls (29.28 versus 21.60 nmol/l; P <0.05) and were statistically significantly correlated with bleeding index (r = 0.321; P <0.05). Plasma osteocalcin concentrations in patients with AgP were higher than those of healthy controls (0.90 versus 0.70 ng/ml; P <0.05). Serum inorganic phosphorus values of both periodontitis groups were lower than those of healthy controls (1.06 +/- 0.18 mmol/l and 1.10 +/- 0.15 mmol/l versus 1.26 +/- 0.17 mmol/l; P <0.05). CONCLUSION Plasma calcifediol levels might be associated with periodontal inflammation.

Initial Periodontal Therapy Reduced Systemic and Local 25-Hydroxy Vitamin D3 and Interleukin-1β in Patients With Aggressive Periodontitis

BACKGROUND 25-hydroxy vitamin D(3) is the major circulating metabolite of vitamin D. Elevated plasma 25-hydroxy vitamin D(3) levels were verified to be associated with generalized aggressive periodontitis (GAgP). In the present study, the influence of initial periodontal therapy on systemic and local levels of 25-hydroxy vitamin D(3) and three related elements (osteocalcin and interleukin-1beta and -6) in patients with GAgP was investigated. METHODS Nineteen patients with GAgP were enrolled. All patients received initial periodontal therapy. Gingival crevicular fluid at two sites of each subject were obtained before therapy and 2 and 6 months after therapy. Plasma was obtained before and 2 months after therapy from 12 of 19 subjects. Systemic and local levels of 25-hydroxy vitamin D(3), osteocalcin, and interleukin-1beta and -6 before and after therapy were measured using radioimmunoassay or enzyme-linked immunosorbent assay kits and compared. RESULTS The respective systemic 25-hydroxy vitamin D(3) and interleukin-1beta levels significantly dropped from baseline to 2 months after therapy (29.28 nmol/l versus 22.50 nmol/l, P = 0.001, and 6.71 ng/l versus 3.23 ng/l, P <0.001, respectively). The respective local 25-hydroxy vitamin D(3) and interleukin-1beta levels significantly decreased from baseline to 2 and 6 months after therapy (8,950 nmol/l versus 5,650 nmol/l versus 3,438 nmol/l, P <0.001, and 10,595 ng/l versus 5,495 ng/l versus 3,960 ng/l, P <0.001, respectively). Systemic and local 25-hydroxy vitamin D(3) concentrations were positively correlated at baseline (r = 0.877; P = 0.022), as was osteocalcin (r = 0.939; P = 0.005). CONCLUSIONS 25-hydroxy vitamin D(3) and interleukin-1beta levels were systemically and locally reduced in patients with GAgP by initial periodontal therapy. 25-hydroxy vitamin D(3) might be involved in periodontal inflammation.

Upregulated Leptin in Periodontitis Promotes Inflammatory Cytokine Expression in Periodontal Ligament Cells.

BACKGROUND Imbalance or disruption in the expression of inflammatory mediators contributes greatly to the breakdown of the periodontal supporting tissues. Leptin, through binding to its receptor (obesity-related leptin and leptin receptor [OBR]), has potent effects on immunity and inflammation. However, to date, researchers only indicated a role of leptin in periodontitis. No direct or valid evidence exists about how leptin and its receptor are regulated by local inflammation, what effects they have, and the underlying mechanisms. METHODS Experimental periodontitis was induced by ligation of mandibular second molars in beagle dogs. The expression of leptin, OBR, and interleukin (IL)-1β was examined by immunohistochemistry. Meanwhile, recombinant human IL-1β was used to stimulate human periodontal ligament cells (hPDLCs) in vitro, and mRNA and protein levels of leptin were measured using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Then, mRNA and protein levels of IL-6 and IL-8 were measured using real-time PCR and ELISA, after stimulation with various concentrations of leptin, knocking down all or only the long form of OBR (OBRb) by small interfering RNA and incubation with multiple intracellular signaling pathway inhibitors, respectively. RESULTS Leptin and OBR increased substantially in inflammatory periodontal tissues, which correlated well with the extent of inflammatory infiltration, and was a result of the upregulation in resident cells themselves. A high dose of leptin could induce the expression of mRNA and protein of IL-6 and IL-8 in hPDLCs through binding with OBRb and activating different intracellular signaling pathways. CONCLUSION Upregulated leptin and OBR in periodontitis stimulated proinflammatory cytokine expression in PDL cells to additionally promote local inflammation.

Influence of rs2228570 on Transcriptional Activation by the Vitamin D Receptor in Human Gingival Fibroblasts and Periodontal Ligament Cells

BACKGROUND rs2228570 is the only known single nucleotide polymorphism of the vitamin D receptor (VDR) that alters the protein structure. VDRs can be distinguished using the restriction endonuclease FokI and accordingly divided into three genotypes: FF, Ff, and ff. Influence of rs2228570 on transcriptional activation by VDRs in human gingival fibroblasts (hGFs) and periodontal ligament cells (hPDLCs) is investigated in this study. METHODS From 15 donors, hGFs and hPDLCs were cultured, genomic DNA was extracted, and genotypes were determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. Cells were stimulated with calcitriol with or without VDR antagonist ZK159222 or osteogenic induction. Alkaline phosphatase, osteocalcin, and VDR messenger RNA (mRNA) expression were detected using real-time PCR. Alkaline phosphatase and osteocalcin protein expression were detected by enzyme activity assays with p-nitrophenyl phosphate substrate and enzyme-linked immunosorbent assay, respectively. RESULTS Among the 15 donor cell cultures, the number of FF, ff, and Ff genotypes were 5, 3, and 7, respectively. There were no significant differences in expression of alkaline phosphatase or osteocalcin among the three genotypes in hGFs. However, after stimulation with calcitriol, alkaline phosphatase and osteocalcin mRNA levels in FF-hPDLCs were significantly higher than in other hPDLCs genotypes, as was osteocalcin protein expression. Furthermore, when ZK159222 was included, this difference disappeared, and when osteogenic induction was performed, alkaline phosphatase and osteocalcin mRNA and protein levels were higher in FF-hPDLCs than in the other hPDLCs genotypes. CONCLUSION The FF-VDR genotype is associated with the most remarkable upregulation of alkaline phosphatase and osteocalcin in hPDLCs.