Impact of non-surgical periodontal treatment on dental anxiety: A comparative study on patients with periodontitis.

Background/purpose: Dental anxiety is prevalent and may result in the avoidance of periodontal therapy and maintenance. This study aimed to explore the impact of non-surgical periodontal treatment (NSPT) on dental anxiety among patients with periodontitis. Materials and methods: In this study, 122 patients with periodontitis participated. The Chinese version of the Modified Dental Anxiety Scale (MDAS) gauged baseline dental anxiety during the initial appointment. Patients receiving non-surgical periodontal treatment (NSPT) in subsequent appointments formed the NSPT group, while those with a delayed NSPT of at least two months constituted the delayed group. In the NSPT group, the second termination questionnaire was administered one month post the last NSPT visit, just before the periodontal re-evaluation. In the delayed group, the second questionnaire was completed before the delayed NSPT initiation. Results: Baseline MDAS scores were comparable between the delay and NSPT groups. However, the NSPT group exhibited lower total scores and scores for each of the five MDAS items at termination compared with the delay group. At baseline, MDAS total scores were inversely associated with age and were lower in males. A reduction in MDAS total scores between observation points was correlated with NSPT, sex, and age after adjustment. Regarding MDAS item 4 (teeth scaled/polished), score reduction consistently correlated with NSPT and age. Conclusion: Participation in NSPT may alleviate dental anxiety, and consequently enhance the patients' conceptiveness to undergo periodontal maintenance or surgery.

Investigating the differences in nutritional status between successfully weaned and unsuccessfully weaned respirator patients.

Long-term respirator users admitted to intensive care units need to be transferred to a respiratory care center (RCC) for weaning. It may cause malnutrition in critical care patients, which may manifest as a reduction in respiratory muscle mass, lower ventilatory capacity, and decreased respiratory tolerance. This study aimed to assess that if the patients' nutritional status were improved, it could help RCC patients to wean from respirators. All participants were recruited from the RCC of a medical foundation in the city and Taipei Tzu Chi Hospital. The indicators include serum albumin level, respirator detachment index, maximum inspiratory pressure (PImax), rapid shallow breathing index, and body composition measurements. We recorded the length of hospital stay, mortality, and RCW (respiratory care ward) referral rate for these participants and analyzed the differences in relevant research indicators between those who were and weren't weaned off. 43 of 62 patients were weaned from respirators, while 19 failed. The resuscitation rate was 54.8%. Patients with respirator weaning had a lower number of RCC admission days (23.1 ± 11.1 days) than respirator-dependent patients (35.6 ± 7.8 days, P < 0.05). The PImax of successfully weaned patients had a greater reduction (- 27.09 ± 9.7 cmH2O) than unsuccessful ones (- 21.4 ± 10.2 cmH2O, P < 0.05). The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of successfully weaned patients (15.8 ± 5.0) were lower than those who were not (20.4 ± 8.4, P < 0.05). There was no significant difference in serum albumin levels between the two groups. In the successfully weaned patients, the serum albumin concentration was increased from 2.2 ± 0.3 to 2.5 ± 0.4 mg/dL, P < 0.05. Improved nutritional status can help RCC patients to wean from respirators.

Accuracy of Implant Placement with a Navigation System, a Laboratory Guide, and Freehand Drilling.

PURPOSE: Computer-aided surgery under navigation system guidance is widely applied in dental implant procedures. However, the accuracy of drilling with such navigation systems has not been comparatively evaluated alongside those of laboratory guide-based and freehand drilling. Therefore, this study aimed to compare the accuracies of these three drilling systems. MATERIALS AND METHODS: A navigation system, a laboratory guide, and freehand drilling were used to drill 150 holes on 30 cast models. Two master models-one each for the maxilla and mandible-were prepared with the idea of placing five implants per cast. After drilling five holes on each cast, postoperative cone beam computed tomography images were acquired to measure the magnitude of errors. RESULTS: The navigation system and laboratory guide were more accurate than freehand placement with respect to total errors at the entry and apex, lateral error at the apex, and angular error. The navigation system was more accurate than the laboratory guide with respect to angular error. Laboratory guide-based drilling was more accurate than freehand drilling in terms of lateral error at entry. CONCLUSION: In comparison with the laboratory guide and freehand placement, the navigation system exhibited lower angular and axial errors. Despite its higher accuracy, the navigation system requires the operator to pay greater attention.

Periodontal status of tooth adjacent to implant with peri-implantitis.

OBJECTIVES: To evaluate the relationship between peri-implantitis and the periodontal health of the adjacent tooth, the periodontal status of the teeth adjacent and contralateral to the implants with and without peri-implantitis. METHODS: Fifty-three subjects with existing dental implants and chronic periodontitis were examined in this cross-sectional study. Seventy implants were categorized into peri-implantitis (n = 42) and healthy/mucositis (n = 28) groups. The periodontal and peri-implant status, including probing depth (PD), clinical attachment level (CAL), and gingival recession (GR) were measured at 6 sites around the implants and the teeth adjacent and contralateral to those implants. In total 560 sites of the 70 teeth/implant sets, the association between the periodontal status at the near and away sites of the teeth (according to implant) and the implant status (without/with peri-implantitis) was examined. RESULTS: A significantly different mean PD (5.01 ±â€¯1.69, 4.42 ±â€¯1.8, 3.55 ±â€¯0.88, and 3.71 ±â€¯1.07 mm, p < 0.001) and CAL (6.02 ±â€¯2.36, 4.89 ±â€¯2.04, 4.35 ±â€¯1.11, and 4.35 ±â€¯1.5 mm, p < 0.001) were noted at the near sites of the teeth adjacent to the implants with peri-implantitis when compared with the away sites of adjacent and contralateral teeth and the near sites of contralateral teeth. With generalized estimating equation (GEE), the presence of peri-implantitis (ß â€¯= 1.041 mm, confidence interval = 0.646-1.435, and p < 0.001; ß â€¯= 0.857 mm, confidence interval = 0.279-1.434, and p < 0.004) and tooth location (ß â€¯= 0.65 mm, confidence interval = 0.4-0.9, and p < 0.001; ß â€¯= 0.682 mm, confidence interval = 0.34-1.024, and p < 0.001) were significantly associated with the values of the PD and CAL of the teeth. Moreover, the factor of examining sites (i.e. near and away sites of the tooth) was significantly associated with CAL (ß = 0.304 mm, confidence interval = 0.019-0.588, and p = 0.036) and GR (ß = 0.136 mm, confidence interval = 0.02-0.252, and p = 0.022). CONCLUSION: The existence of peri-implantitis, the tooth location, and the examining site are significantly associated with the periodontal measurements of the remaining teeth. CLINICAL SIGNIFICANCE: Peri-implant health is related to the periodontal health of the natural teeth close to the dental implant.

Cyclosporine A enhances gingival ß-catenin stability via Wnt signaling.

BACKGROUND: Cyclosporine A (CsA) increases ß-catenin messenger RNA (mRNA) and protein expression. The present study demonstrates that Wnt/ß-catenin signaling inhibits ß-catenin degradation in the gingiva. METHODS: Forty 5-week-old male Sprague-Dawley rats were assigned to two study groups after healing from right maxillary molar extractions. The rats in the experimental group were fed 30 mg/kg CsA daily for 4 weeks, whereas the control rats were fed mineral oil. At the end of the study, all rats were sacrificed, and the gingivae were obtained. The gingival morphology after CsA treatment was evaluated by histology, and the genes related to Wnt/ß-catenin signaling were initially screened by microarray. Polymerase chain reaction, Western blotting, and immunohistochemistry were used to examine the mRNA and protein expression of proliferating cell nuclear antigen, cyclin D1, E-cadherin, ß-catenin, Dvl-1, glycogen synthase kinase-3ß, axin-1, and adenomatous polyposis coli (APC). Phosphoserine and ubiquitinylated ß-catenin were detected after immunoprecipitation. RESULTS: In rats treated with CsA, overgrowth of gingivae was observed, and altered expression of genes related to Wnt/ß-catenin signaling was detected by the microarray. The gingival mRNA and protein expression profiles for genes associated with Wnt/ß-catenin signaling further confirmed the effect of CsA: ß-catenin and Dvl-1 expression increased, but APC and axin-1 expression decreased. Western blotting and immunohistochemistry showed decreases in ß-catenin serine phosphorylation (33/37) and ubiquitinylation in the gingivae of CsA-treated rats. CONCLUSION: CsA-enhanced gingival ß-catenin stability may be involved in gene upregulation or ß-catenin degradation via the Wnt/ß-catenin pathway.

Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium.

BACKGROUND: It has been proposed that cyclosporin A (CsA) may induce epithelial-to-mesenchymal transition (EMT) in gingiva. The aims of the present study are to confirm the notion that EMT occurs in human gingival epithelial (hGE) cells after CsA treatment and to investigate the role of transforming growth factor beta1 (TGF-ß1) on this CsA-induced EMT. METHODS: The effects of CsA, with and without TGF-ß1 inhibitor, on the morphologic changes of primary culture of hGE cells were examined in vitro. The changes of protein and messenger RNA (mRNA) expressions of two EMT markers (E-cadherin and alpha-smooth muscle actin) in the hGE cells after CsA treatment with and without TGF-ß1 inhibitor were evaluated with immunocytochemistry and real-time polymerase chain reaction. RESULTS: The epithelial cells became spindle-like, elongated, and disassociated from neighboring cells and lost their original cobblestone monolayer pattern when CsA was added. However, the epithelial cells stayed in their original cobblestone morphology with treatment of TGF-ß1 inhibitor on top of the CsA treatment. When CsA was given, the protein and mRNA expressions of E-cadherin and α-SMA were significantly altered, and these alterations were significantly reversed with pretreatment of TGF-ß1 inhibitor. CONCLUSIONS: CsA could induce Type 2 EMT in gingiva by changing the morphology of epithelial cells and altering the EMT markers/effectors. The CsA-induced gingival EMT is dependent or at least partially dependent on TGF-ß1.

Effects of enamel matrix derivative on the proliferation and osteogenic differentiation of human gingival mesenchymal stem cells.

INTRODUCTION: Gingiva-derived mesenchymal stem cells (GMSCs) have recently been harvested and applied for rebuilding lost periodontal tissue. Enamel matrix derivative (EMD) has been used for periodontal regeneration and the formation of new cementum with inserting collagen fibers; however, alveolar bone formation is minimal. Recently, EMD has been shown to enhance the proliferation and mineralization of human bone marrow mesenchymal stem cells. Because the gingival flap is the major component to cover the surgical wound, the effects of EMD on the proliferation and mineralization of GMSCs were evaluated in the present study. METHODS: After single cell suspension, the GMSCs were isolated from the connective tissues of human gingiva. The colony forming unit assay of the isolated GMSCs was measured. The expression of stem cell markers was examined by flow cytometry. The cellular telomerase activity was identified by polymerase chain reaction (PCR). The osteogenic, adipogenic and neural differentiations of the GMSCs were further examined. The cell proliferation was determined by MTS assay, while the expression of mRNA and protein for mineralization (including core binding factor alpha, cbfα-1; alkaline phosphatase, ALP; and osteocalcin, OC; ameloblastin, AMBN) were analyzed by real time-PCR, enzyme activity and confocal laser scanning microscopy. RESULTS: The cell colonies could be easily identified and the colony forming rates and the telomerase activities increased after passaging. The GMSCs expressed high levels of surface markers for CD73, CD90, and CD105, but showed low expression of STRO-1. Osteogenic, adipogenic and neural differentiations were successfully induced. The proliferation of GMSCs was increased after EMD treatment. ALP mRNA was significantly augmented by treating with EMD for 3 hours, whereas AMBN mRNA was significantly increased at 6 hours after EMD treatment. The gene expression of OC was enhanced at the dose of 100 µg/ml EMD at day 3. Increased protein expression for cbfα-1 at day 3, for ALP at day 5 and 7, and for OC at week 4 after the EMD treatments were observed. CONCLUSIONS: Human GMSCs could be successfully isolated and identified. EMD treatments not only induced the proliferation of GMSCs but also enhanced their osteogenic differentiation after induction.

Epigallocatechin-3-gallate attenuates Porphyromonas gingivalis lipopolysaccharide-enhanced matrix metalloproteinase-1 production through inhibition of interleukin-6 in gingival fibroblasts.

BACKGROUND: Recent studies have shown that epigallocatechin-3-gallate (EGCG), a major constituent of green tea extract, exhibits effects of anti-inflammation and antioxidation on periodontal inflammation. The present in vitro study examines the effect of EGCG on Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS)-enhanced expression of interleukin (IL)-6 and matrix metalloproteinase (MMP)-1, as well as the activation of nuclear factor-kappa B (NF-κB). Furthermore, the role of IL-6 on LPS-enhanced MMP-1 production is evaluated using human gingival fibroblasts (HGFs). METHODS: HGFs were primary cultured from human gingiva specimens. The cytotoxicities of EGCG and LPS were tested by cell viability tests. The cellular mRNA expression of IL-6 was determined by reverse-transcription polymerase chain reaction, and the protein expression of MMP-1 and IL-6 was examined by enzyme-linked immunosorbent assay. The cytosol expression and nuclear translocation of NF-κB was evaluated by immunocytochemistry followed by confocal laser scanning microscopy. RESULTS: Pg LPS significantly increased MMP-1 production in HGFs, whereas adding EGCG significantly attenuated this enhanced production of MMP-1. LPS treatment also increased the mRNA and protein expression of IL-6 and stimulated NF-κB activation in HGFs. However, the addition of EGCG significantly attenuated the IL-6 expression and NF-κB activation. Supplemental addition of IL-6 significantly enhanced cellular MMP-1 production, whereas anti-IL-6 antibody inhibited LPS-enhanced MMP-1 production. CONCLUSION: EGCG could attenuate Pg LPS-enhanced production of MMP-1 in HGFs, whereas this attenuation might be due to the inhibition of IL-6 by EGCG.

Berberine's effect on periodontal tissue degradation by matrix metalloproteinases: an in vitro and in vivo experiment.

Periodontal disease involves tissue destruction caused by interactions among bacterial antigens and inflammatory mediators including matrix metalloproteinases (MMPs). Berberine, an isoquinoline alkaloid isolated from medicinal herbs, can inhibit the degradative action of extracellular MMPs. The effect of berberine on the periodontal expression of MMPs was examined in vitro and in vivo. Gelatinolytic activity of pro-MMP-2, MMP-2, and MMP-9 in the human gingival fibroblast and/or U-937 was compared after treatment with Porphyromonas gingivalis lipopolysaccharide (P.g. LPS) in four medias containing 0, 1, 10 and 100µM of berberine each. Twelve animals were divided into three groups for the study: (A) non-ligation, (B) ligation, and (C) ligation-plus-berberine (75mg/kg berberine by gastric lavage daily); and the effect of berberine on periodontal destruction was evaluated in the ligature-induced periodontitis in rats for 8 days by micro computerized tomography (micro-CT), histology and immunohistochemistry (IHC). An enhancing effect of P.g. LPS on MMP activities was identified, with a greater effect on fibroblasts/U937 co-culture than on either culture alone. When berberine was added to the LPS-treated cultures, the activities of MMPs were significantly reduced in dose-dependent manner. In the animals, the trends of the following parameters were compared. 1. Micro-CT distances between cemento-enamel junction (CEJ) and dental alveolar bone crest: B>C>A. 2. Histometrically measured crest bone levels: B>C>A. 3. Amount of collagen deposited in tissue areas: A>C>B. 4. Attachment loss: B>C≈A. 5. Connective tissue (CT) attachment: B>either A or C. 6. Expression of cells stained positive for MMP-2 and -9 by IHC: B>C>A. In conclusion, berberine demonstrated in vitro an inhibitory effect on P.g. LPS-enhanced MMP activities of HGF and U937 macrophages, reducing in vivo gingival tissue degradation in periodontitic rats. We thus propose that berberine may slow periodontal degradation through the regulation of MMPs in periodontitis induced by bacterial plaque.

Effects of bone morphogenetic protein-6 on periodontal wound healing/regeneration in supraalveolar periodontal defects in dogs.

OBJECTIVE: Application of a synthetic BMP-6 polypeptide in a rat periodontal fenestration defect model enhanced periodontal wound healing/regeneration including new bone and cementum formation. The purpose of this study was to translate the relevance of these initial observations into a discriminating large animal model. METHODS: Critical-size (4-5 mm) supraalveolar periodontal defects were created at the 2(nd) and 3(rd) mandibular premolar teeth in 11 Beagle dogs. Experimental sites received BMP-6 at 0.25, 1.0 and 2.0 mg/ml soak-loaded onto an absorbable collagen sponge (ACS) carrier or ACS alone (control) each condition repeated in four jaw quadrants. The animals were euthanized at 8 weeks when block biopsies were collected and processed for histologic/histometric analysis. RESULTS: BMP-6 at 0.25, 1.0 and 2.0 mg/ml soak-loaded onto the ACS yielded significantly enhanced new bone (0.99 ± 0.07 versus 0.23 ± 0.13 mm/BMP-6 at 0.25 mg/ml) and cementum (2.45 ± 0.54 versus 0.73 ± 0.15 mm/BMP-6 at 0.25 mg/ml) formation including a functionally oriented periodontal ligament compared with control (p < 0.05). A significant inverse linear association between BMP-6 dose and new bone (ß = -0.21 ± 0.09 mm, p = 0.016) and cementum height (ß = -0.34 ± 0.15 mm, p = 0.023) was observed. Minimal root resorption was observed without significant differences between groups. Ankylosis was not observed for any of the experimental groups. CONCLUSIONS: Surgical application of BMP-6/ACS onto critical-size supraalveolar defects enhanced periodontal wound healing/regeneration, in particular cementogenesis including a functionally oriented periodontal ligament; the low BMP-6 0.25 mg/ml concentration apparently providing the most effective dose.

Upregulation of the expression of epidermal growth factor and its receptor in gingiva upon cyclosporin A treatment.

BACKGROUND: To understand the roles of epidermal growth factor (EGF) and EGF receptor (EGF-R) in cyclosporin A (CsA)-induced gingival overgrowth, expression of EGF and EGF-R upon CsA treatment was examined in an oral epidermoid carcinoma cell line of humans (OECM-1) and in edentulous gingiva of rats. METHODS: In vitro study: after CsA treatment, OECM-1 cells were harvested to evaluate their mRNA and protein expression of EGF and EGF-R with reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry (ICC). In vivo study: 3 weeks after extraction of all maxillary molars, 20 male Sprague-Dawley rats were assigned to a CsA group (30 mg/kg, fed daily) and a control group. Five rats per group were sacrificed at weeks 1 and 4. Edentulous ridge specimens were obtained for evaluating their mRNAs and protein expression with RT-PCR, real-time RT-PCR, and immunohistochemistry (IHC). In both in vitro and in vivo experiments, the proliferating potential of epithelial cells was examined by the presence of proliferating cell nuclear antigen (PCNA). RESULTS: In vitro: dose-dependently increased mRNA expression of EGF and EGF-R in OECM-1 cells was noted after CsA treatment. Protein expressions of EGF and EGF-R were higher in OECM-1 with CsA treatment than without CsA. In vivo: higher mRNA and protein expressions of EGF and EGF-R were also observed in the gingival tissues of CsA-treated rats. In both in vitro and in vivo experiments, greater PCNA expression after CsA treatment was demonstrated. CONCLUSIONS: Higher expression of EGF and EGF-R upon CsA therapy was observed in OECM-1 epithelial cells of humans and in edentulous gingiva of rats. We suggest that CsA could upregulate gene and protein expression of EGF and EGF-R, and the upregulation may play a role in gingival overgrowth.

Upregulation of transforming growth factor-beta1 and vascular endothelial growth factor gene and protein expression in cyclosporin-induced overgrown edentulous gingiva in rats.

BACKGROUND: To examine the effects of cyclosporin A (CsA) on the expression of growth factors in induced gingival overgrowth with limited contributing factors arising from local inflammation caused by bacterial plaque, this study of gingival overgrowth was designed on the edentulous ridge of rats. METHODS: After a 3-week healing period following maxillary molar extractions, 16 five-week-old male Sprague-Dawley rats were assigned to CsA and control groups. Animals in the CsA group were fed 30 mg/kg CsA daily, whereas the control rats received a mineral oil vehicle instead. After 4 weeks, all animals were sacrificed, and the morphology of edentulous ridges was recorded by dental impression. The gingivae on the left-hand side were dissected and stored for mRNA analysis, whereas the gingivae on the right-hand side were fixed in 4% paraformaldehyde for immunohistochemistry (IHC) analysis of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor beta (PDGF-beta), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF). RESULTS: The edentulous gingivae were enlarged and the body weights were reduced in the CsA-treated animals compared to controls. The mRNA expressions of TGF-beta1, IGF-1, and VEGF were higher in the gingivae of the CsA group than in the control group. In addition, a greater mRNA expression (7.21-fold) of VEGF was demonstrated in the CsA group than in the control group by real-time polymerase chain reaction (PCR). The percentages of cells staining positive for TGF-beta1 and VEGF were significantly greater in the CsA rats than in the control rats. CONCLUSIONS: Greater mRNA expression and positive staining for TGF-beta1 and VEGF were observed in the edentulous gingivae of rats that received CsA. Therefore, CsA may upregulate TGF-beta1 and VEGF gene expression and protein secretion in CsA-induced gingival overgrowth.

Effects of bone morphogenetic protein-6 on periodontal wound healing in a fenestration defect of rats.

BACKGROUND: Bone morphogenetic proteins (BMPs) may play significant roles in bone formation. The ability of BMP-6 to promote wound healing has been chosen as the subject of this investigation. In this study, a synthetic rat BMP-6 polypeptide was applied to a periodontal fenestration defect in rats to elucidate the effects of BMP-6 on periodontal wound healing. MATERIAL AND METHODS: Following surgery to create a bony window on the buccal aspects of mandibular molar roots, 24 male Sprague Dawley rats were divided into four groups according to BMP application (0, 1, 3 and 10 microg, respectively). Animals were killed after 28 days and the mandible taken for histological examination. Histometric measurements were performed on sections selected from three levels (coronal, middle and apical levels; with 240 microm apart from the central) of the defect. New bone and cementum formation (including area and thickness) were analyzed and compared. RESULTS: In general, minimal new bone was observed on the surgically created defects in the non-BMP group, whereas a complete osseous healing occurred in all BMP-6 treated animals. New bone formation (both in area and thickness) was significantly influenced by both the dosage and the examining level, whereas new cementum formation was affected by dosage only. An increase in bone and cementum formation was noted in all three BMP groups when compared with the control group at all examined levels. Among the BMP groups, greatest new bone and cementum formation were noted in the 3 microg group. New cementum thickness increased on the cementum surfaces of the defects compared with the dentinal surfaces in all study groups. CONCLUSION: An increase in new bone and cementum formation was noted after applying a synthetic BMP-6 polypeptide to a periodontal fenestration defect in rats. Therefore, we suggest that BMP-6 may play a certain role in periodontal regeneration.

Effects of CD14 receptors on tissue reactions induced by local injection of two gram-negative bacterial lipopolysaccharides.

Lipopolysaccharide (LPS) was recognized by CD14, which may be an important mediator in the deleterious effects of LPS on the periodontal destruction. To investigate the roles of CD14 molecules on LPS-induced soft tissue inflammation and bone destruction, the tissues of CD14-deficient mice were examined histopathologically following a local injection of either Salmonella minnesota or Porphyromonas gingivalis LPS. In the first group, 12 mice received a local injection of 500 microg of purified P. gingivalis LPS and six mice were injected with saline to the calvaria as controls. In the second group 13 mice were injected subcutaneously on the laterally abdominal skin with 50 microg of S. minnesota LPS and three mice were injected with PBS. Mice were sacrificed at day 5. After histological preparation, the tissue sections of calvaria and soft tissue specimen were stained with tartrate-resistant acid phosphatase (TRAP) marker for osteoclast and macrophage. The soft tissue sections were also stained with hematoxylin & eosin (H&E). Resorption surface and osteoclast index were measured to quantify bone resorption. Necrotic area and inflammatory cell numbers were estimated to assess the situation of local inflammation. Our results indicated that LPS-induced bone resorption is inhibited in CD14-deficient mice. An increase in the number of total inflammatory cells was noticed in both CD14-deficient mice and wild-type mice; however, the cell numbers were less in CD14-deficient mice than those in wild-type mice (two- to three-fold decrease). Therefore, we conclude that the LPS-stimulated bone resorption is mainly via CD14 receptor but the LPS-induced soft tissue inflammation appears to be partially dependent on the receptor.

The role of interleukin-1beta in Porphyromonas gingivalis lipopolysaccharide-induced bone resorption.

BACKGROUND: Pro-Interleukin (IL)-1beta is not fully active after synthesis. It acquires activity after secretion when cleaved with a specific intracellular protease, IL-1beta converting enzyme (ICE). ICE-deficient animals display impaired production of IL-1beta. Upon stimulation with lipopolysaccharide (LPS), ICE homozygous deficiency mutants are highly resistant to endotoxic shock. Lipopolysaccharides have also been identified as major bacterial factors in bone resorption. However, the exact mechanisms by which LPS stimulates bone resorption in ICE-deficient animals are still uncertain. The present study investigated how interleukin-1beta activity mediates LPS-induced bone resorption in vivo. METHODS: In our dose-dependent experiment, 10 six-week-old ICE-deficient mice were divided into two groups and injected with one of two concentrations of P gingivalis (A7436) LPS: 500 microg and 100 microg. Ten wild-type mice (164BBC) served as the control subjects. Frozen sections of calvaria were stained with tartrate-resistant acid phosphatase (TRAP) for histomorphometric analysis to quantify osteoclast number, area, and activity. RESULTS: Inhibition of 38% in osteoclast index and osteoclast surface was observed in 500 microg LPS-induced ICE-deficient mice compared with the wild-type mice. However, the data were not significantly different between these two groups at 100 microg of LPS injection, but they were still higher than those of control subjects. Bone-resorbing activities of the osteoclast showed no significant differences between ICE-deficient mice and wild-type mice. CONCLUSIONS: Within limitations of the study, we suggest that LPS-induced bone resorption may be caused by enhancing osteoclastogenesis, not by increasing osteoclast resorbing activity. The LPS leading bone resorption is, at least, partially mediated by IL-1beta at higher concentrations.