Publications by authors named "Jianxia Hou"

35 Publications

Pro-inflammatory cytokine interleukin-6-induced hepcidin, a key mediator of periodontitis-related anemia of inflammation.

J Periodontal Res 2021 Mar 3. Epub 2021 Mar 3.

Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Objectives: To investigate whether anemia of inflammation (AI) occurs in periodontitis patients and to further explore underlying pathogenesis of periodontitis-related AI by an experimental periodontitis model.

Background: Previous studies have reported periodontitis patients could show a tendency toward AI. However, the relationship between periodontitis and AI remains unclear, and the related pathological mechanisms have not been identified.

Materials And Methods: Periodontal clinical parameters, inflammatory markers, and anemia-related indicators were compared between 98 aggressive periodontitis (AgP) patients and 103 healthy subjects. An experimental periodontitis model was induced by ligature placement in mice. The changes in mice inflammatory markers, anemia indicators, hepcidin mRNA expression, and serum hepcidin concentrations were measured. Human and mouse liver cells were treated with interleukin-6 (IL-6) for analyzing the changes in hepcidin expression based on mRNA and protein levels.

Results: AgP patients exhibited higher white blood cell counts, IL-6, and C-reactive protein. Adjusted linear regression analyses showed correlations between AgP and decreased hemoglobin (HGB) and hematocrit (HCT). The ligature-induced periodontitis caused systemic inflammation and elevated IL-6 levels. Lower red blood cell counts, HGB, and HCT were detected, whereas the levels of hepcidin mRNA expression and serum hepcidin concentrations increased. The treatment of hepatocytes with IL-6 induced both hepcidin mRNA expression and hepcidin secretion.

Conclusions: Systemic inflammation induced by periodontitis leads to an increased risk for AI. IL-6-induced hepcidin could play a central mediator role and act as a key pathologic mechanism. Our results demonstrate periodontitis may be considered as an additional inflammatory disease contributing to the development of AI.
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http://dx.doi.org/10.1111/jre.12865DOI Listing
March 2021

Two-Way MR-Forest Based Growing Path Classification for Malignancy Estimation of Pulmonary Nodules.

IEEE J Biomed Health Inform 2021 Feb 8;PP. Epub 2021 Feb 8.

This paper proposes a two-way multi-ringed forest (TMR-Forest) to estimating the malignancy of the pulmonary nodules for false positive reduction (FPR). Based on our previous work of deep decision framework, named MR-Forest, we generate a growing path mode on predefined pseudo-timeline of L time slots to build pseudo-spatiotemporal features. It synchronously works with FPR based on MR-Forest to help predict the labels from a dynamic perspective. Concretely, Mask R-CNN is first used to recommend the bounding boxes of ROIs and classify their pathological features. Afterward, hierarchical attribute matching is introduced to obtain the input ROIs' attribute layouts and select the candidates for their growing path generation. The selected ROIs can replace the fixed-sized ROIs' fitting results at different time slots for data augmentation. A two-stage counterfactual path elimination is used to screen out the input paths of the cascade forest. Finally, a simple label selection strategy is executed to output the predicted label to point out the input nodule's malignancy. On 1034 scans of the merged dataset, the framework can report more accurate malignancy labels to achieve a better CPM score of 0.912, which exceeds those of MR-Forest and 3DDCNNs about 2.8% and 4.7%, respectively.
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http://dx.doi.org/10.1109/JBHI.2021.3057627DOI Listing
February 2021

Histological, radiological, and clinical outcomes of sinus floor elevation using a lateral approach for pre-/post-extraction of the severely compromised maxillary molars: a study protocol for a randomized controlled trial.

Trials 2021 Jan 28;22(1):101. Epub 2021 Jan 28.

Department of Periodontology, Peking University Hospital and School of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.

Background: The volume of residual alveolar bone is critical to the survival of dental implants. When the volume of alveolar bone in the posterior maxillary region is less than 4 mm, maxillary sinus floor elevation (MSFE) with the lateral approach is an effective option. Traditionally, this standard approach is usually conducted at 4-6 months after tooth extraction (standard MSFE). However, defective dentition due to extraction can impair mastication during the period of bone remodeling, especially if the molars on both sides are severely compromised and must be extracted. MSFE before extraction (modified MSFE) can take full advantage of residual tooth strength. However, the effectiveness and practicability of the modified MSFE procedure remain unknown. Therefore, the aim of this study was to compare the clinical outcomes of modified vs. standard MSFE, in order to provide references to periodontists.

Methods/design: The study cohort included 25 adult patients (50 surgery sites) recruited from Peking University Hospital and School of Stomatology who met the inclusion criteria. The two sides of each patient will be randomly divided into two groups: a test group-modified MSFE or a control group-standard MSFE. The surgical duration and patient-reported outcomes (visual analog scale for discomfort) will be documented. Clinical indicators, including implant survival rates, mucosal conditions, and complications, will be recorded every 6 months during the 5-year follow-up period. The volume of the alveolar bone and marginal bone level will be assessed radiographically (cone-beam CT and periapical films) every 6 months. Histological analysis of biopsy samples retrieved from both sides will be performed to evaluate the biological features of the bone.

Discussion: The current study will explore the implant survival rates, safety, reliability, effectiveness, and practicability of the modified MSFE procedure. Moreover, the extent of osteogenesis on the sinus floor will also be assessed. The results of this trial will provide strategies for the modified MSFE procedure to achieve ideal clinical outcomes.

Trial Registration: International Clinical Trials Registry Platform ChiCTR1900020648 . Registered on 1 January 2019.
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http://dx.doi.org/10.1186/s13063-021-05047-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844904PMC
January 2021

Expression of vitamin D 1α-hydroxylase in human gingival fibroblasts in vivo.

PeerJ 2021 4;9:e10279. Epub 2021 Jan 4.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

Background: Vitamin D 1α-hydroxylase CYP27B1 is the key factor in the vitamin D pathway. Previously, we analyzed the expression of CYP27B1 in human gingival fibroblasts in vitro. In the present study, we analyzed the gingival expression of CYP27B1 in vivo.

Methods: Forty-two patients with periodontitis Stage IV Grade C and 33 controls were recruited. All patients with periodontitis had unsalvageable teeth and part of the wall of the periodontal pocket was resected and obtained after tooth extraction. All controls needed crown-lengthening surgery, and samples of gingiva resected during surgery were also harvested. All the individuals' gingivae were used for immunohistochemistry and immunofluorescence. In addition, gingivae from seventeen subjects of the diseased group and twelve subjects of the control group were analyzed by real-time PCR.

Results: Expression of CYP27B1 was detected both in gingival epithelia and in gingival connective tissues, and the expression in connective tissues colocalized with vimentin, indicating that CYP27B1 protein is expressed in gingival fibroblasts. The expression of CYP27B1 mRNA in gingival connective tissues and the CYP27B1 staining scores in gingival fibroblasts in the diseased group were significantly higher than those in the control group.

Conclusions: Expression of CYP27B1 in human gingival tissues was detected, not only in the fibroblasts of gingival connective tissues, but also in the gingival epithelial cells, and might be positively correlated with periodontal inflammation.
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http://dx.doi.org/10.7717/peerj.10279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789863PMC
January 2021

Modified minimally invasive surgical technique plus Bio-Oss Collagen for regenerative therapy of isolated interdental intrabony defects: study protocol for a randomised controlled trial.

BMJ Open 2020 12 10;10(12):e040046. Epub 2020 Dec 10.

Department of Periodontology, Peking University School and Hospital of Stomatology and National Engineering Laboratory for Digital and Material Technology of Stomatology and Beijing Key Laboratory of Digital Stomatology, Beijing, China

Introduction: Periodontal regeneration surgery has been widely used to deal with intrabony defects. Modified minimally invasive surgical technique (M-MIST) is designed to deal with isolated interdental intrabony defects, and has achieved satisfactory periodontal regenerative effect. Bio-Oss Collagen, as a bioactive material, has been applied for periodontal regeneration. It is similar to human cancellous bone, with the ability to promote bone formation; furthermore, it has exceptional plasticity and spatial stability. The combination of different materials and techniques has become a research hotspot in recent years. By combining the superiority of regeneration technology and materials, better regenerative effect can be achieved. This study will search for differences between M-MIST combined with Bio-Oss Collagen, and M-MIST alone in regeneration therapy for intrabony defects.

Methods And Analysis: The present research is designed as a two-group parallel randomised controlled trial. The total number of patients is 40. The patients will be randomly assigned to two groups, with 20 participants in each group, for further periodontal regenerative surgery. Test group: M-MIST plus Bio-Oss Collagen.

Control Group: M-MIST. After 12 months, the measurement indices will be recorded; these will include clinical attachment gain and radiographical intrabony defect depth change as the primary results, and secondary outcomes of full-mouth plaque scores, probing depth, full-mouth bleeding scores, gingival recession, mobility, gingival papilla height and Visual Analogue Scale. The paired samples t-test will be applied to detect any difference between baseline and 1-year registrations. A general linear model will be performed to study the relationship between the secondary and the primary outcome.

Ethics And Dissemination: The present research has received approval from the Ethics Committee of Peking University School and Hospital of Stomatology (PKUSSIRB-202053002). Data of the present research will be registered with the International Clinical Trials Registry Platform. Additionally, we will disseminate the results through scientific dental journals.

Trial Registration Number: ChiCTR-2000030851.

Protocol Version: Protocol Version 4, 14 July 2020.
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http://dx.doi.org/10.1136/bmjopen-2020-040046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733185PMC
December 2020

Comparison of peri-implant submucosal microbiota in arches with zirconia or titanium implant-supported fixed complete dental prostheses: a study protocol for a randomized controlled trial.

Trials 2020 Nov 27;21(1):979. Epub 2020 Nov 27.

Department of Periodontology, Peking University School and Hospital of Stomatology; National Engineering Laboratory for Digital and Material Technology of Stomatology; Research Center of Engineering and Technology for Digital Dentistry of Ministry of Health; Beijing Key Laboratory of Digital Stomatology, No. 22, Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.

Background: The success rate of implant-supported prostheses for edentulous patients is relatively high. However, the incidence of biological complications, especially peri-implant mucositis and peri-implantitis, increases yearly after the placement of prostheses. The accumulation of pathogenic bacteria adjacent to a prosthesis is the main cause of biological complications. Titanium, one of the classical materials for implant-supported prostheses, performs well in terms of biocompatibility and ease of maintenance, but is still susceptible to biofilm formation. Zirconia, which has emerged as an appealing substitute, not only has comparable properties, but presents different surface properties that influence the adherence of oral bacteria. However, evidence of a direct effect on oral flora is limited. Therefore, the aim of the present study was to assess the effects of material properties on biofilm formation and composition.

Methods: The proposed study is designed as a 5-year randomized controlled trial. We plan to enroll 44 edentulous (mandible) patients seeking full-arch, fixed, implant-supported prostheses. The participants will be randomly allocated to one of two groups: group 1, in which the participants will receive zirconia frameworks with ceramic veneering, or group 2, in which the participants will receive titanium frameworks with acrylic resin veneering. Ten follow-up examinations will be completed by the end of this 5-year trial. Mucosal conditions around the implants will be recorded every 6 months after restoration. Peri-implant submucosal plaque will be collected at each reexamination, and bacteria flora analysis will be performed with 16S rRNA gene sequencing technology in order to compare differences in microbial diversity between groups. One week before each visit, periodontal maintenance will be arranged. Each participant will receive an X-ray examination every 12 months as a key index to evaluate the marginal bone level around the implants.

Discussion: The current study aims to explore the oral microbiology of patients following dental restoration with zirconia ceramic frameworks or titanium frameworks. The features of the microbiota and the mucosal condition around the two different materials will be evaluated and compared to determine whether zirconia is an appropriate material for fixed implant-supported prostheses for edentulous patients.

Trial Registration: International Clinical Trials Registry Platform (ICTRP) ChiCTR2000029470. Registered on 2 February 2020. http://www.chictr.org.cn/searchproj.aspx?
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http://dx.doi.org/10.1186/s13063-020-04853-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694361PMC
November 2020

Extending the vitamin D pathway to vitamin D and CYP27A1 in periodontal ligament cells.

J Periodontol 2020 Oct 26. Epub 2020 Oct 26.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

Background: In periodontal connective tissue cells, the vitamin D pathway has been elucidated, and vitamin D in the main storage form, 25-hydroxy vitamin D (25[OH]D ), and the functional form, 1,25-dihydroxy vitamin D (1,25[OH] D ), have been found to induce the expression of human cationic antimicrobial protein (hCAP-18)/LL-37. Moreover, synergistic effects between Toll-like receptor agonists and 25(OH)D have been reported. This research aimed at extending the vitamin D pathway to vitamin D and CYP27A1 in human periodontal ligament cells (hPDLCs) to further explore its function in periodontal inflammatory reaction.

Methods: Vitamin D was used to stimulate hPDLCs in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS). Conversely, CYP27A1 RNA interference was performed to further validate the findings. The mRNA expression of hCAP-18 was determined with real-time polymerase chain reaction. Monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) were also detected. The cell supernatant levels of LL-37 were detected with enzyme-linked immunosorbent assay.

Results: Vitamin D significantly enhanced the generation of hCAP-18/LL-37. A combination of Pg-LPS and vitamin D significantly promoted hCAP-18/LL-37 expression. When the expression of CYP27A1 was knocked down with RNA interference, the induction of hCAP-18/LL-37 expression was significantly inhibited. Therefore, the mRNA levels of MCP-1 and IL-8 in hPDLCs were significantly decreased through the vitamin D pathway.

Conclusion: The vitamin D pathway from vitamin D to hCAP-18/LL-37 exists in hPDLCs, and CYP27A1 might be involved in periodontal immune defense.
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http://dx.doi.org/10.1002/JPER.20-0225DOI Listing
October 2020

Calprotectin levels in gingival crevicular fluid and serum of patients with chronic periodontitis and type 2 diabetes mellitus before and after initial periodontal therapy.

J Periodontal Res 2021 Jan 16;56(1):121-130. Epub 2020 Sep 16.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

Background: This study is aimed to compare the total amount of calprotectin in gingival crevicular fluid (GCF) and the concentration of calprotectin in serum among the patients with type 2 diabetes mellitus and chronic periodontitis (DM-P), the patients with chronic periodontitis (CP) and the healthy controls, as well as the variation of these indicators before and three months after the initial periodontal therapy for the DM-P patients.

Methods: 35 patients with DM-P patients, 32 patients with CP patients, and 43 healthy controls were recruited. Calprotectin levels in serum and GCF, periodontal parameters, fasting blood glucose (FBG), and HbA1c were measured at baseline for all the groups and three months after the initial periodontal therapy for the DM-P patients.

Results: At baseline, the calprotectin levels in GCF and serum were the highest in DM-P, followed by CP, and the lowest in healthy controls. GCF calprotectin was significantly and positively correlated with serum calprotectin and probing depth (PD), while serum calprotectin had a significant positive correlation with GCF calprotectin and HbA1c. Periodontal parameters, HbA1c, and serum and GCF calprotectin became significantly reduced after the initial periodontal treatment. The reduction of serum calprotectin was consistent with that of HbA1c, while the decrease of GCF calprotectin was in agreement with that of PD, attachment loss (AL), and bleeding on probing (BOP).

Conclusions: The levels of calprotectin in serum and GCF in the DM-P patients are significantly higher than those in CP patients and healthy controls, which significantly reduced 3 months after the initial periodontal therapy. Furthermore, it suggests diabetic patients might exhibit more pronounced inflammation periodontally and systemically.
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http://dx.doi.org/10.1111/jre.12800DOI Listing
January 2021

Morphometric evaluation of the alveolar bone around central incisors during surgical orthodontic treatment of high-angle skeletal class III malocclusion.

Orthod Craniofac Res 2021 Feb 29;24(1):87-95. Epub 2020 Jul 29.

Department of Orthodontics, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, China.

Objectives: To evaluate morphometric characteristics of alveolar bone around the incisors of high-angle skeletal class III patients receiving surgical orthodontic treatment.

Setting And Sample Population: Thirty high-angle skeletal class III patients (mean age, 20.94 ± 3.25 years) underwent cone-beam computed tomography before treatment (T0), after pre-surgical orthodontic treatment (T1) and after treatment (T2).

Materials And Methods: The vertical bone level (VBL), alveolar bone thickness (ABT), alveolar bone area (ABA) and position of upper and lower central incisors (UCIs and LCIs) were evaluated. The ABT included five levels (4, 6, 8 mm from the cemento-enamel junction, midroot and root apex level). One-way repeated measures ANOVA with Bonferroni's multiple-comparison test and matched t test was performed to compare variables.

Results: Before treatment, the average labial ABT was approximately 1 mm in UCIs and 0.38 ~ 0.79 mm in LCIs, and the VBL of the LCIs was over 2 mm. After treatment, the VBL increased by 2.19 ± 1.96 mm (P < .001) on the lingual side of UCIs and 2.78 ± 2.29 mm and 3.09 ± 2.52 mm on the labial and lingual sides of LCIs, respectively (all P < .001). ABT at every level decreased significantly, decreasing by 1.66 ± 1.93 mm at the 8 mm level of UCIs and 1.06 ± 1.01 mm at the apex of LCIs (P < .001). The lingual ABA of UCIs and LCIs decreased by over 50% (P < .001).

Conclusions: In high-angle skeletal class III patients, the condition of alveolar bone around UCIs and LCIs was extremely poor before treatment. Further alveolar bone resorption occurred during surgical orthodontic treatment. More attention should be paid to the movement of anterior teeth in cases of severe alveolar bone loss.
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http://dx.doi.org/10.1111/ocr.12408DOI Listing
February 2021

A digital technique for splinting periodontally compromised mobile teeth in the mandibular anterior region.

J Prosthet Dent 2021 Apr 12;125(4):560-563. Epub 2020 May 12.

Professor, Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Research Center of Engineering and Technology for Digital Dentistry of Ministry of Health, Beijing Key Laboratory of Digital Stomatology, Beijing, PR China. Electronic address:

A digital technique for fabricating a periodontal splint is presented. The lingual surface of periodontally compromised mandibular anterior teeth is captured and registered to form the emergence profile of the periodontal splint. An accurate periodontal splint is fabricated for mandibular anterior teeth with increased mobility after scaling and root planing.
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http://dx.doi.org/10.1016/j.prosdent.2020.03.004DOI Listing
April 2021

Platelets as inflammatory mediators in a murine model of periodontitis.

J Clin Periodontol 2020 05 12;47(5):572-582. Epub 2020 Mar 12.

Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Aim: To investigate the role of platelets during the development of ligature-induced experimental periodontitis in mice.

Materials And Methods: Experimental periodontitis was induced by placement of sterilized 5-0 cotton ligatures around the maxillary and mandibular second molars of C57BL/6 wild-type mice. Flow cytometry was used to analyse platelet activation and platelet-leucocyte aggregate formation, and histologic analysis was used to evaluate inflammation and localization of platelets and leucocytes in periodontal tissues during the development of experimental periodontitis and in experimental periodontitis with and without antiplatelet drug treatment.

Results: Experimental periodontitis induced platelet activation and platelet-leucocyte interaction. Platelets and leucocytes gradually infiltrated in inflammatory gingival tissues during the development of experimental periodontitis. The inhibition of platelet activation via drug therapy led to significant inhibition of leucocyte migration and marked reduction in periodontal inflammation.

Conclusion: This study revealed that platelets are critical for inflammation and tissue injury in periodontitis and serve as mediators of inflammation in periodontal tissue.
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http://dx.doi.org/10.1111/jcpe.13265DOI Listing
May 2020

Clinical evaluation of ultrasonic subgingival debridement versus ultrasonic subgingival scaling combined with manual root planing in the treatment of periodontitis: study protocol for a randomized controlled trial.

Trials 2020 Jan 28;21(1):113. Epub 2020 Jan 28.

Department of Periodontology, Peking University School and Hospital of Stomatology and National Engineering Laboratory for Digital and Material Technology of Stomatology and Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China.

Background: Periodontal diseases are regarded as the most common diseases of mankind. The prevalence rate of periodontal disease assumes a clear growth tendency, increasing by 57.3% from 1990 to 2010. Thereby, effective periodontal therapy is still a long-term task and a difficult problem. The goals of periodontal therapy are to eliminate the infectious and inflammatory processes of periodontal diseases. Root planing, in order to eliminate the "infected cementum," has been an important step in the treatment of periodontitis since the 1970s. However, along with the understanding of the effects of endotoxin on the root surface, the necessity of manual root planing has been gradually queried. Ultrasonic instruments, which are more recent innovations, would not remove the cementum excessively, and are also more time-saving and labor-saving compared to using hand instruments. Hence, an increasing number of dentists prefer to do scaling with ultrasonic instruments only. However, the necessity of root planing remains emphasized in the international mainstream views of periodontal mechanical treatment. Therefore, this study is devoted to compare the clinical effect of ultrasonic subgingival debridement and ultrasonic subgingival scaling combined with manual root planing, which takes the implementation of root planing as the only variable and is more in line with the current clinical situation, thus hoping to provide some valuable reference to dentists.

Methods/design: Forty adult patients who fit the inclusion criteria are being recruited from the Peking University Hospital of Stomatology (Beijing, China). By means of randomization tables, one quadrant of the upper and lower teeth is the test group and the other is the control group. Test group: ultrasonic subgingival scaling combined with manual root planing.

Control Group: ultrasonic subgingival debridement. In a 24-week follow-up period, plaque index, probing depth, clinical attachment loss, bleeding index, furcation involvement, mobility, and patient-reported outcome (Visual Analog Scale for pain and sensitivity) will be observed and documented.

Discussion: This study evaluates the effectiveness of ultrasonic subgingival scaling combined with manual root planing and ultrasonic subgingival debridement alone in the nonsurgical treatment of periodontitis with a split-mouth design after 1, 3 and 6 months. The result of the trial should potentially contribute to an advanced treatment strategy for periodontitis with an ideal clinical outcome.

Trial Registration: International Clinical Trials Registry Platform (ICTRP), ID: ChiCTR1800017122. Registered on 12 July 2018.
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http://dx.doi.org/10.1186/s13063-019-4031-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988244PMC
January 2020

Preliminary investigation on the molecular mechanisms underlying the correlation between VDR-FokI genotype and periodontitis.

J Periodontol 2020 03 21;91(3):403-412. Epub 2020 Feb 21.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.

Background: The only polymorphism that could change the protein structure in vitamin D receptor (VDR) is the FokI polymorphism (rs2228570). The FF genotype has the strongest transcriptional activity of VDR and is correlated with higher susceptibility to periodontitis. To reveal the possible molecular mechanisms for the correlation preliminarily, the influence of VDR-FokI genotype on the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) in human gingival fibroblasts (hGFs) and human periodontal ligament cells (hPDLCs) was investigated in this study.

Methods: hGFs and hPDLCs from 15 donors (five FF, seven Ff, and three ff) were treated with 1,25OH D , with or without the specific knockdown of VDR using siRNA. The mRNA and protein expression of OPG and RANKL were detected using real-time PCR and enzyme-linked immunosorbent assay, respectively.

Results: Both in hGFs and hPDLCs, 1,25OH D could significantly induce the mRNA and protein expression of RANKL, and FF genotype had significantly higher induction than the other genotypes, however, neither 1,25OH D nor VDR-FokI had significant influence on the OPG expression. As a result, the RANKL/OPG ratio was significantly elevated under 1,25OH D stimulation and FF genotype had the most remarkable elevation. When VDR was knocked down, all the differences among the three genotypes disappeared.

Conclusion: The strongest transcriptional activity of FF genotype might contribute to the strongest enhancement of RANKL expression and RANKL/OPG ratio in hGFs and hPDLCs stimulated by 1,25OH D , which might help to reveal the mechanisms of the correlation between FF genotype and susceptibility to periodontitis.
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http://dx.doi.org/10.1002/JPER.19-0368DOI Listing
March 2020

Ferritin expression in the periodontal tissues of primates.

Eur J Histochem 2019 Sep 3;63(3). Epub 2019 Sep 3.

Peking University School and Hospital of Stomatology.

Ferritin, an iron-binding protein, is composed of two subunits, a heavy chain and a light chain. It regulates many biological functions, such as proliferation, angiogenesis, and immunosuppression. The objective of this study was to determine the expression and distribution of ferritin in the periodontal tissuesof primates.First, we assessed the expression of ferritin in primary cultured cells isolated from human periodontal tissues using the polymerase chain reaction and immunofluorescent staining. Second, we investigated the expression and distribution of ferritin in the periodontal tissues of Macaca fascicularis, human gingival tissues, and human gingival carcinoma tissues using immunohistochemistry.Both protein and mRNA of ferritin were constitutively present in human primary cultured cells, including those from the dental apical papilla, periodontal ligament, dental pulp, and gingival epithelium, as well as gingival fibroblasts. In M. fascicularistissues, the immunohistochemical staining was particularly strong in blood vessel and mineralizing areas of the dental pulp and periodontal ligament. Ferritin heavy chain exhibited specific immunopositivity in in the stratum basale of the epithelium in human gingival tissue and strong immunostaining was found in peripheral regions of gingival carcinoma sites. Ferritin is constitutivelypresent andwidelydistributed in the periodontal tissues of primates. Ferritin may play roles in epithelial proliferation, vascular angiogenesis, and mineralization in these tissues.
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http://dx.doi.org/10.4081/ejh.2019.3046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755262PMC
September 2019

Up-regulated ferritin in periodontitis promotes inflammatory cytokine expression in human periodontal ligament cells through transferrin receptor via ERK/P38 MAPK pathways.

Clin Sci (Lond) 2019 01 11;133(1):135-148. Epub 2019 Jan 11.

Department of Periodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, P.R. China

Objective: Ferritin, an iron-binding protein, is ubiquitous and highly conserved; it plays a crucial role in inflammation, which is the main symptom of periodontitis. Full-length cDNA library analyses have demonstrated abundant expression of ferritin in human periodontal ligament. The aims of the present study were to explore how ferritin is regulated by local inflammation, and to investigate its functions and mechanisms of action in the process of periodontitis.

Methods: Human gingival tissues were collected from periodontitis patients and healthy individuals. Experimental periodontitis was induced by ligature of second molars in mice. The expression of ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH) were assessed by immunohistochemistry. Meanwhile, after stimulating human periodontal ligament cells (HPDLCs) with -lipopolysaccharide (LPS), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α), the expression of FTH and FTL were measured. Then, IL-6 and IL-8 were measured after incubation with different concentrations of apoferritin (iron-free ferritin) and several intracellular signaling pathway inhibitors, or after knockdown of the transferrin receptor.

Results: Both FTH and FTL were substantially higher in inflamed periodontal tissues than in healthy tissues. The location of the elevated expression correlated well with the extent of inflammatory infiltration. Moreover, expression of FTH and FTL were enhanced after stimulation with -LPS, IL-6, TNF-α. Apoferritin induced the production of IL-6 and IL-8 in a dose-dependent manner partly through binding to the transferrin receptor and activating ERK/P38 signaling pathways in HPDLCs.

Conclusions: Ferritin is up-regulated by inflammation and exhibits cytokine-like activity in HPDLCs inducing a signaling cascade that promotes expression of pro-inflammatory cytokines associated with periodontitis.
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http://dx.doi.org/10.1042/CS20180679DOI Listing
January 2019

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

J Periodontol 2017 09 11;88(9):915-925. Epub 2017 May 11.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, PR China.

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.
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http://dx.doi.org/10.1902/jop.2017.170030DOI Listing
September 2017

The role of platelets in inflammatory immune responses in generalized aggressive periodontitis.

J Clin Periodontol 2017 02 9;44(2):150-157. Epub 2017 Jan 9.

Department of Periodontology, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Aim: To investigate the relationship between inflammatory markers and platelet size in generalized aggressive periodontitis (GAgP).

Material And Methods: Periodontal, inflammatory and platelet indices were compared between 59 GAgP patients and 59 healthy subjects. Gingival biopsies from five patients and five healthy subjects were examined by immunohistochemistry and electron microscopy. Changes in patient periodontal and platelet indices were re-evaluated at 3 months after periodontal therapy.

Results: Platelet size was decreased significantly in GAgP patients compared to healthy subjects (p ≤ 0.003). Weak negative correlations between platelet size and periodontal parameters were found in GAgP patients (p ≤ 0.025). Platelet aggregates and adhesion to the endothelium or leucocytes were found in venules and connective tissues of gingival biopsies from GAgP patients. Mean platelet volume (MPV) and platelet large cell ratio increased after periodontal therapy in GAgP patients (p ≤ 0.038). The increase in MPV was related to the decrease in bleeding index in GAgP patients after periodontal therapy (p < 0.001; r = 0.357).

Conclusion: Platelet size was reduced in GAgP patients compared to healthy controls, possibly due to the consumption of large platelets at sites of periodontal inflammation. Platelets may be involved in host responses to periodontal infection in GAgP.
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http://dx.doi.org/10.1111/jcpe.12657DOI Listing
February 2017

Platelet activation and platelet-leukocyte interaction in generalized aggressive periodontitis.

J Leukoc Biol 2016 11 22;100(5):1155-1166. Epub 2016 Jun 22.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

Generalized aggressive periodontitis (GAgP) is an inflammatory disease of host response to bacterial challenge. To explore the role of platelets in host-microbial interactions in patients with periodontitis, 124 patients with GAgP and 57 healthy subjects were enrolled. Reliable indicators of subclinical platelet functional status, platelet count (PLT), platelet large cell ratio (PLCR), and mean platelet volume (MPV), were significantly lower in the GAgP group than in the control group and were negatively correlated with clinical periodontal parameters. The levels of important cytosolic protein in neutrophils, calprotectin (S100A8/A9) in plasma, and gingival crevicular fluid (GCF) were significantly higher in patients with GAgP compared with healthy subjects. Moreover, the GCF calprotectin level was negatively correlated with PLCR and MPV values. To explore the possible mechanisms of changes in platelet indices in periodontitis, flow cytometry analysis was performed, and patients with GAgP were found to have a higher status of platelet activation compared with healthy controls. Porphyromonas gingivalis (P. gingivalis) and recombinant human S100A8/A9 (rhS100A8/A9) induced platelet activation and facilitated platelet-leukocyte aggregate formation in whole blood of healthy subjects. In response to P. gingivalis and rhS100A8/A9, platelets from patients with GAgP increased activation and increased formation of platelet-leukocyte aggregates compared with those from healthy subjects. Platelet aggregates and platelets attached to leukocytes were found on gingival tissues from patients with GAgP, suggesting that decreased platelet size and count in the circulation might be related to consumption of large, activated platelets at inflamed gingiva. Platelets may have a previously unrecognized role in host response to periodontal infection.
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http://dx.doi.org/10.1189/jlb.4A1115-526RRDOI Listing
November 2016

Six Degree-of-Freedom Haptic Simulation of Probing Dental Caries Within a Narrow Oral Cavity.

IEEE Trans Haptics 2016 Apr-Jun;9(2):279-91. Epub 2016 Feb 18.

Haptic simulation of handling pathological tissues is a crucial component to enhance virtual surgical training systems. In this paper, we introduce a configuration-based optimization approach to simulate the exploration and diagnosis of carious tissues in dental operations. To simulate the six Degree-of-Freedom (6DoF) haptic interaction between the dental probe and the oral tissues, we introduce two interaction states, the sliding state and the penetration state, which simulate the exploration on the surface of and inside of the caries, respectively. Penetration criteria considering a contact force threshold are defined to trigger the switch between the two states. By utilizing a simplified friction model based on the optimization approach, various multi-region frictional contacts between the probe and carious tissues are simulated. To simulate the exploration within the carious tissues for diagnosing the depth of the caries, a dynamic sphere tree is used to constrain the insertion/extraction of the probe within carious tissues along a fixed direction while enabling simulation of additional contacts of the probe with neighboring oral tissues during the insertion/extraction process. Experimental results show that decays with different levels of stiffness and friction coefficients can be stably simulated. Preliminary user studies show that users could easily identify the invisible boundary between the decay and healthy tissues and correctly rank the depth of target decays within a required time limit. The proposed approach could be used for training delicate motor skill of probing target carious teeth in a narrow oral cavity, which requires collaborated control of tool posture and insertion/extraction force, while avoiding damages to adjacent healthy tissues of the tongue and gingiva.
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http://dx.doi.org/10.1109/TOH.2016.2531660DOI Listing
October 2017

S100A9-induced release of interleukin (IL)-6 and IL-8 through toll-like receptor 4 (TLR4) in human periodontal ligament cells.

Mol Immunol 2015 Oct 31;67(2 Pt B):223-32. Epub 2015 May 31.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, PR China. Electronic address:

S100A8, S100A9, and calprotectin (the S100A8/S100A9 complex) are calcium-binding proteins that promote extracellular pro-inflammatory functions and may play an important role in periodontal disease. Both toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE) are thought to be important receptors for S100A8, S100A9, and calprotectin, but the specific pathways in periodontal ligament (PDL) cells are not yet clear. Our study was designed to identify the specific receptors for S100A9 in human PDL cells. Additionally, we investigated the specific pathways that activate the secretion of pro-inflammatory cytokines interleukins (IL)-6 and IL-8 in PDL cells. The role of nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) in S100A9-induced pro-inflammatory cytokines were investigated through western blot analysis, dichlorodihydrofluorescein diacetate (H2DCFDA) probe and the application of specific pathway inhibitors. Our results suggest that the S100A9-induced release of IL-6 and IL-8 from human PDL cells is dependent on TLR4, but not RAGE. We provide evidence that S100A9 promotes the secretion of IL-6 and IL-8 through different pathways. Specifically, S100A9 up-regulates the secretion of IL-6 from human PDL cells through NF-κB and p38 pathways and up-regulates the release of IL-8 from human PDL cells through the NF-κB, extracellular-regulated kinase (ERK) 1/2, c-Jun amino-terminal kinase (JNK) 1/2, and p38 signaling pathways. In addition, the release of both cytokines depends on ROS production. The release of both cytokines depends on ROS production. These results suggest that S100A9 promotes pro-inflammatory responses in PDL cells through the TLR4-mediated NF-κB and MAPK signaling pathways.
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http://dx.doi.org/10.1016/j.molimm.2015.05.014DOI Listing
October 2015

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

J Periodontol 2015 Jul 16;86(7):917-26. Epub 2015 Apr 16.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

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.
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http://dx.doi.org/10.1902/jop.2015.150030DOI Listing
July 2015

F33: A-: B-, IncHI2/ST3, and IncI1/ST71 plasmids drive the dissemination of fosA3 and bla CTX-M-55/-14/-65 in Escherichia coli from chickens in China.

Front Microbiol 2014 16;5:688. Epub 2014 Dec 16.

Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University Guangzhou, China.

The purpose of this study was to examine the occurrence of fosfomycin-resistant Escherichia coli from chickens and to characterize the plasmids carrying fosA3. A total of 661 E. coli isolates of chicken origin collected from 2009 to 2011 were screened for plasmid-mediated fosfomycin resistance determinants by PCR. Plasmids were characterized using PCR-based replicon typing, plasmid multilocus sequence typing, and restriction fragment length polymorphisms. Associated addiction systems and resistance genes were identified by PCR. PCR-mapping was used for analysis of the genetic context of fosA3. Fosfomycin resistance was detected in 58 isolates that also carried the fosA3 gene. Fifty-seven, 17, and 52 FosA3-producers also harbored bla CTX-M, rmtB, and floR genes, respectively. Most of the 58 fosA3-carrying isolates were clonally unrelated, and all fosA3 genes were located on plasmids belonged to F33:A-:B- (n = 18), IncN-F33:A-:B- (n = 7), IncHI2/ST3 (n = 10), IncI1/ST71 (n = 3), IncI1/ST108 (n = 3), and others. The genetic structures, IS26-ISEcp1-bla CTX-M-55-orf477-bla TEM-1-IS26-fosA3-1758bp-IS26 and ISEcp1-bla CTX-M-65-IS903-iroN-IS26-fosA3-536bp-IS26 were located on highly similar F33:A-:B- plasmids. In addition, bla CTX-M-14-fosA3-IS26 was frequently present on similar IncHI2/ST3 plasmids. IncFII plasmids had a significantly higher frequency of addiction systems (mean 3.5) than other plasmids. Our results showed a surprisingly high prevalence of fosA3 gene in E. coli isolates recovered from chicken in China. The spread of fosA3 can be attributed to horizontal dissemination of several epidemic plasmids, especially F33:A-:B- plasmids. Since coselection by other antimicrobials is the major driving force for the diffusion of the fosA3 gene, a strict antibiotic use policy is urgently needed in China.
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http://dx.doi.org/10.3389/fmicb.2014.00688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267423PMC
January 2015

The pro-apoptotic and pro-inflammatory effects of calprotectin on human periodontal ligament cells.

PLoS One 2014 22;9(10):e110421. Epub 2014 Oct 22.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, P.R. China.

Calprotectin, a heterodimer of S100A8 and S100A9 subunits, is associated with inflammatory disorders such as rheumatoid arthritis and cystic fibrosis. Although calprotectin levels are increased significantly in the gingival crevicular fluid (GCF) of periodontitis patients, its effects on periodontal ligament cells (PDLCs) remain largely unknown. The aim of this study was to evaluate calprotectin levels in the GCF of generalized aggressive periodontitis (AgP) patients and to investigate the effects of recombinant human calprotectin (rhS100A8/A9) and its subunits (rhS100A8 and rhS100A9) in PDLCs. Both the concentration and amount of crevicular calprotectin were significantly higher in the AgP group compared with healthy controls. In addition, the GCF calprotectin levels were correlated positively with clinical periodontal parameters including bleeding index, probing depth, and clinical attachment loss. rhS100A8/A9 promoted cell apoptosis, whereas rhS100A8 and rhS100A9 individually exerted little effect on apoptosis in PDLCs. rhS100A9 and rhS100A8/A9 increased the activation of nuclear factor-κB (NF-κB) by promoting the nuclear translocation of p65 in PDLCs, subsequently inducing expression of the pro-inflammatory cytokines IL-6, IL-8, TNFα, and COX2. Treatment with an NF-κB inhibitor partially reversed the rhS100A9- and rhS100A8/A9-induced upregulation of the pro-inflammatory cytokines. rhS100A9, and not rhS100A8, was mainly responsible for the pro-inflammatory role of calprotectin. Collectively, our results suggest that calprotectin promotes apoptosis and the inflammatory response in PDLCs via rhS100A9. These findings might help identify novel treatments for periodontitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0110421PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206420PMC
June 2015

A histological and biomechanical study of bone stress and bone remodeling around immediately loaded implants.

Sci China Life Sci 2014 Jun 13;57(6):618-26. Epub 2014 May 13.

Key Lab for Biomechanics and Mechanobiology of Ministry of Education, School of Biological and Medical Engineering, Beihang University, Beijing, 100191, China.

Immediate loading (IL) increases the risk of marginal bone loss. The present study investigated the biomechanical response of peri-implant bone in rabbits after IL, aiming at optimizing load management. Ninety-six implants were installed bilaterally into femurs of 48 rabbits. Test implants on the left side created the maximal initial stress of 6.9 and 13.4 MPa in peri-implant bone and unloaded implants on the contralateral side were controls. Bone morphology and bone-implant interface strength were measured with histological examination and push-out testing during a 12-week observation period. Additionally, the animal data were incorporated into finite element (FE) models to calculate the bone stress distribution at different levels of osseointegration. Results showed that the stress was concentrated in the bone margin and the bone stress gradually decreased as osseointegration proceeded. A stress of about 2.0 MPa in peri-implant bone had a positive effect on new bone formation, osseointegration and bone-implant interface strength. Bone loss was observed in some specimens with stress exceeding 4.0 MPa. Data indicate that IL significantly increases bone stress during the early postoperative period, but the load-bearing capacity of peri-implant bone increases rapidly with an increase of bone-implant contact. Favorable bone responses may be continually promoted when the stress in peri-implant bone is maintained at a definite level. Accordingly, the progressive loading mode is recommended for IL implants.
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http://dx.doi.org/10.1007/s11427-014-4657-7DOI Listing
June 2014

Leptin and its receptor expression in dental and periodontal tissues of primates.

Cell Tissue Res 2014 Jan 15;355(1):181-8. Epub 2013 Oct 15.

Department of Periodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing, 100081, People's Republic of China,

Leptin and its receptor (OBR) have attracted much attention since their discovery. They have been reported to play central roles in energy balance, the immune-inflammatory response and bone metabolism. Evidence indicates that leptin and OBR are associated with inflammatory diseases of dental and periodontal tissues. The first step for establishing this is to determine the expression of leptin and OBR in these tissues. Our study is the first to examine systematically the expression of leptin and OBR in dental and periodontal tissues of monkeys (Macaca fascicularis) by immunohistochemistry and in primary cultured cells, isolated from human dental and periodontal tissues, by reverse transcription plus the polymerase chain reaction and immunocytochemistry. Our results show that leptin and OBR are constitutively expressed and widely distributed in dental and periodontal tissues of primates. Their immunoreaction is especially strong in junctional epithelium, a unique front-line defense around teeth and in mineralizing areas of the dental pulp and periodontal ligament. The expression of the long and also functional form of OBR (OBRb) indicates that leptin has a direct effect on these cells. Thus, we can reasonably infer that leptin and OBR exert effects on defense, mineralization and angiogenesis in dental and periodontal tissues of primates.
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http://dx.doi.org/10.1007/s00441-013-1729-0DOI Listing
January 2014

Activity of 25-hydroxylase in human gingival fibroblasts and periodontal ligament cells.

PLoS One 2012 12;7(12):e52053. Epub 2012 Dec 12.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

Background: We previously demonstrated that 25-hydroxyvitamin D(3) concentrations in gingival crevicular fluid are 300 times higher than those in the plasma of patients with aggressive periodontitis. Here we explored whether 25-hydroxyvitamin D(3) can be synthesized by periodontal soft tissue cells. We also investigated which of the two main kinds of hydroxylases, CYP27A1 and CYP2R1, is the key 25-hydroxylase in periodontal soft tissue cells.

Methodology/principal Findings: Primary cultures of human gingival fibroblasts and periodontal ligament cells from 5 individual donors were established. CYP27A1 mRNA, CYP2R1 mRNA and CYP27A1 protein were detected in human gingival fibroblasts and periodontal ligament cells, whereas CYP2R1 protein was not. After incubation with the 25-hydroxylase substrate vitamin D(3), human gingival fibroblasts and periodontal ligament cells generated detectable 25-hydroxyvitamin D(3) that resulted in the production of 1α,25-dihydroxyvitamin D(3). Specific knockdown of CYP27A1 in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 25-hydroxyvitamin D(3) and 1α,25-dihydroxyvitamin D(3) production. Knockdown of CYP2R1 did not significantly influence 25-hydroxyvitamin D(3) synthesis. Sodium butyrate did not influence significantly CYP27A1 mRNA expression; however, interleukin-1β and Porphyromonas gingivalis lipopolysaccharide strongly induced CYP27A1 mRNA expression in human gingival fibroblasts and periodontal ligament cells.

Conclusions: The activity of 25-hydroxylase was verified in human gingival fibroblasts and periodontal ligament cells, and CYP27A1 was identified as the key 25-hydroxylase in these cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052053PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520845PMC
September 2013

Detection of the plasmid-encoded fosfomycin resistance gene fosA3 in Escherichia coli of food-animal origin.

J Antimicrob Chemother 2013 Apr 28;68(4):766-70. Epub 2012 Nov 28.

College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, South China Agricultural University (SCAU), Guangzhou, People's Republic of China.

Objectives: To investigate the occurrence of plasmid-mediated fosfomycin resistance genes among Escherichia coli from food animals in China.

Methods: A total of 892 E. coli isolates collected from individual pigs (n=368), chickens (n=196), ducks (n=261), geese (n=35), pigeons (n=20) and partridges (n=12) in Guangdong Province during 2002-08 were screened for the presence of fosA3, fosA and fosC2 by PCR amplification and sequencing. The clonal relationship of fosA3-positive isolates, plasmid content and other associated resistance genes were also characterized.

Results: Twelve (1.3%) E. coli isolates showed resistance to fosfomycin and 10 (1.1%) isolates (4 from pigs, 2 from chickens, 2 from ducks, 1 from a goose and 1 from a pigeon) were positive for fosA3. None of the E. coli isolates was positive for fosA or fosC2. All of the isolates carrying fosA3 were CTX-M producers, and three of them carried rmtB. Most of the fosA3-harbouring isolates were found to be clonally unrelated. The fosA3 genes were flanked by IS26. Two fosA3 genes co-localized with rmtB and blaCTX-M-65 on indistinguishable F33:A-:B- plasmids that carried three addiction systems (pemI/pemK, hok/mok/sok and srnB). Four, one and one fosA3 genes were found to be associated with IncN (ST8 type), IncI1 and F2:A-:B- plasmids, respectively.

Conclusions: We discovered that fosA3 is always associated with blaCTX-M, which facilitates its quick dispersal. The emergence of fosA3 in food animals could impact on human medicine by the potential transfer of resistance through the food chain.
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http://dx.doi.org/10.1093/jac/dks465DOI Listing
April 2013

Complete nucleotide sequence of pHN7A8, an F33:A-:B- type epidemic plasmid carrying blaCTX-M-65, fosA3 and rmtB from China.

J Antimicrob Chemother 2013 Jan 14;68(1):46-50. Epub 2012 Sep 14.

College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, SCAU, South China Agricultural University, Guangzhou, People's Republic of China.

Objectives: To characterize a representative self-transmissible multidrug resistance plasmid pHN7A8 isolated from an Escherichia coli from a dog in China, classified as F33:A-:B- by replicon sequence typing and carrying the bla(TEM-1b), bla(CTX-M-65), fosA3 and rmtB genes conferring resistance to penicillins, cephalosporins, fosfomycin and aminoglycosides, respectively.

Methods: pHN7A8 was sequenced using a whole-genome shotgun approach and the sequence analysed by comparison with reference plasmids.

Results: pHN7A8 is a circular molecule of 76 878 bp. bla(CTX-M-65), fosA3 and rmtB are found in known contexts, interspersed with different mobile elements including ISEcp1, IS1, Tn2, IS1294, IS903 and four copies of IS26. This multiresistance region has only a single nucleotide difference from that of pXZ, an F2:A-:B- plasmid isolated from poultry in China. The pHN7A8 backbone carries genes encoding addiction and partitioning systems that promote plasmid maintenance and has a similar organization to pXZ, as well as IncFII plasmids such as R100, pC15-1a/pEK516 and pHK23, isolated in Japan, Canada/the UK and China, respectively, but with varying levels of identity, suggesting recombination.

Conclusions: pHN7A8 is a chimera that may have resulted from the acquisition, by recombination in the plasmid backbone, of the multiresistance region found in pXZ. This region appears to have evolved from the resistance determinant R100 through the stepwise integration of multiple antimicrobial resistance determinants from different sources by the actions of mobile elements and recombination. The successful dissemination of this multidrug resistance plasmid presents further challenges for the prevention and treatment of Enterobacteriaceae infections.
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http://dx.doi.org/10.1093/jac/dks369DOI Listing
January 2013

Role of ferritin in the cytodifferentiation of periodontal ligament cells.

Biochem Biophys Res Commun 2012 Oct 11;426(4):643-8. Epub 2012 Sep 11.

Department of Periodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.

This study investigated the expression and functions of ferritin, which is involved in osteoblastogenesis, in the periodontal ligament (PDL). The PDL is one of the most important tissues for maintaining the homeostasis of teeth and tooth-supporting tissues. Real-time PCR analyses of the human PDL revealed abundant expression of ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH), which encode the highly-conserved iron storage protein, ferritin. Immunohistochemical staining demonstrated predominant expression of FTL and FTH in mouse PDL tissues in vivo. In in vitro-maintained mouse PDL cells, FTL and FTH expressions were upregulated at both the mRNA and protein levels during the course of cytodifferentiation and mineralization. Interestingly, stimulation of PDL cells with exogenous apoferritin (iron-free ferritin) increased calcified nodule formation and alkaline phosphatase activity as well as the mRNA expressions of mineralization-related genes during the course of cytodifferentiation. On the other hand, RNA interference of FTH inhibited the mineralized nodule formation of PDL cells. This is the first report to demonstrate that ferritin is predominantly expressed in PDL tissues and positively regulates the cytodifferentiation and mineralization of PDL cells.
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http://dx.doi.org/10.1016/j.bbrc.2012.09.008DOI Listing
October 2012

Characterization of the autocrine/paracrine function of vitamin D in human gingival fibroblasts and periodontal ligament cells.

PLoS One 2012 25;7(6):e39878. Epub 2012 Jun 25.

Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.

Background: We previously demonstrated that 25-hydroxyvitamin D(3), the precursor of 1α,25-dihydroxyvitamin D(3), is abundant around periodontal soft tissues. Here we investigate whether 25-hydroxyvitamin D(3) is converted to 1α,25-dihydroxyvitamin D(3) in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1α,25-dihydroxyvitamin D(3) in periodontal soft tissue cells.

Methodology/principal Findings: We established primary cultures of human gingival fibroblasts and human periodontal ligament cells from 5 individual donors. We demonstrated that 1α-hydroxylase was expressed in human gingival fibroblasts and periodontal ligament cells, as was cubilin. After incubation with the 1α-hydroxylase substrate 25-hydroxyvitamin D(3), human gingival fibroblasts and periodontal ligament cells generated detectable 1α,25-dihydroxyvitamin D(3) that resulted in an up-regulation of CYP24A1 and RANKL mRNA. A specific knockdown of 1α-hydroxylase in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 1α,25-dihydroxyvitamin D(3) production and mRNA expression of CYP24A1 and RANKL. The classical renal regulators of 1α-hydroxylase (parathyroid hormone, calcium and 1α,25-dihydroxyvitamin D(3)) and Porphyromonas gingivalis lipopolysaccharide did not influence 1α-hydroxylase expression significantly, however, interleukin-1β and sodium butyrate strongly induced 1α-hydroxylase expression in human gingival fibroblasts and periodontal ligament cells.

Conclusions/significance: In this study, the expression, activity and functionality of 1α-hydroxylase were detected in human gingival fibroblasts and periodontal ligament cells, raising the possibility that vitamin D acts in an autocrine/paracrine manner in these cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382579PMC
January 2013