Obesity, Bone Loss, and Periodontitis: The Interlink.
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ABSTRACT:
SUBMITTER: Zhao P
PROVIDER: S-EPMC9313439 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Clinical studies have shown that metabolic syndrome (MetS) is associated with increased risk of developing periodontitis. However, the underlying mechanisms remain largely unknown. Since it is known that lipopolysaccharide (LPS)-activated toll-like receptor 4 signaling pathways play a crucial role in periodontitis, we hypothesized that MetS enhances LPS-induced periodontal inflammation and alveolar bone loss. In this study, we induced MetS in C57BL/6 mice by feeding them high-fat diet (HFD), and we induced periodontitis by periodontal injection of Aggregatibacter actinomycetemcomitans LPS. We found that mice fed a HFD had significantly increased body weight, plasma lipids, insulin, and insulin resistance when compared with mice fed regular chow, indicating that the mice developed MetS. We also found that a HFD markedly increased LPS-induced alveolar bone loss, osteoclastogenesis, and inflammatory infiltration. Analysis of gene expression in periodontal tissue revealed that HFD and LPS injection cooperatively stimulated expression of cytokines that are known to be involved in periodontal tissue inflammation and osteoclastogenesis-such as interleukin 6, monocyte-chemotactic protein 1, receptor activator of nuclear factor kappa-B ligand, and macrophage colony-stimulating factor. To further understand the potential mechanisms involved in MetS-boosted tissue inflammation, our in vitro studies showed that palmitic acid-the most abundant saturated fatty acid (SFA) and the major SFA in the HFD used in our animal study-potently enhanced LPS-induced proinflammatory gene expression in macrophages. In sum, this study demonstrated that MetS was associated with increased periodontal inflammation and alveolar bone loss in an LPS-induced periodontitis animal model. This study also suggests that SFA palmitic acid may play an important role in MetS-associated periodontitis by enhancing LPS-induced expression of inflammatory cytokines in macrophages.
| S-EPMC4300302 | biostudies-other
Project description:B10 cells can regulate inflammatory responses in innate immunity. Toll-like receptors (TLRs) play an important role in B cell-mediated immune responses in periodontal disease. This study aimed to determine the effects of TLR-activated B10 cells on periodontal bone loss in experimental periodontitis. Spleen B cells isolated from C57BL/6J mice were cultured with Porphyromonas gingivalis lipopolysaccharide (LPS) and cytosine-phospho-guanine (CpG) oligodeoxynucleotides for 48 h. B10-enriched CD1dhi CD5+ B cells were sorted by flow cytometry and were adoptively transferred to recipient mice through tail vein injection. At the same time, P. gingivalis-soaked ligatures were placed subgingivally around the maxillary second molars and remained there for 2 weeks before the mice were euthanized. Interleukin-10 (IL-10) production and the percentage of CD1dhi CD5+ B cells were significantly increased with treatment with P. gingivalis LPS plus CpG compared to those in mice treated with P. gingivalis LPS or CpG alone. Mice with CD1dhi CD5+ B cell transfer demonstrated reduced periodontal bone loss compared to the no-transfer group and the group with CD1dlo CD5- B cell transfer. Gingival IL-10 mRNA expression was significantly increased, whereas expressions of receptor activator of NF-?B ligand (RANKL)/osteoprotegerin (OPG), tumor necrosis factor alpha (TNF-?), and IL-1? were significantly inhibited in the CD1dhi CD5+ B cell transfer group. The percentages of CD19+ IL-10+ cells, CD19+ CD1dhi CD5+ cells, and P. gingivalis-binding CD19+ cells were significantly higher in recovered mononuclear cells from gingival tissues of the CD1dhi CD5+ B cell transfer group than in tissues of the no-transfer group and the CD1dlo CD5- B cell transfer group. This study indicated that the adoptive transfer of B10 cells alleviated periodontal inflammation and bone loss in experimental periodontitis in mice.
| S-EPMC5563573 | biostudies-literature
Project description:The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1?, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis.
| S-EPMC4959623 | biostudies-literature
Project description:To characterize in rice rats: (a) periodontitis (PD) progress with feeding of standard laboratory rat chow (STD) during ages 4-80 weeks; and (b) PD progress with feeding of a high sucrose-casein (H-SC) diet during young adulthood.One group (N=12) was euthanized at age 4 weeks (Baseline). Four groups (N=8-16) consumed a STD diet from baseline and were necropsied at ages 22, 30, 52, and 80 weeks. Three groups (N=10-16) consumed an H-SC diet from baseline. Two were necropsied at ages 22 and 30 weeks, respectively. The third switched to the STD diet at age 22 weeks and was necropsied at age 30 weeks. All mandibles/maxillae were assessed by histometry for degree of periodontal inflammation (PD Score), alveolar crest height (ACH, mm), and horizontal alveolar bone height (hABH, mm2).In STD diet rats aged ?30 weeks, all endpoints were worse (P<0.05) than at Baseline. In H-SC diet rats aged ?22 weeks, all endpoints were worse than at Baseline (P<0.05). At age 22 weeks, all endpoints were worse in the H-SC group than in the STD group (P<0.05). By age 30 weeks, the STD and H-SC groups did not differ.1) STD diet fed rice rats develop moderate/severe PD by age 30 weeks; 2) an H-SC diet accelerates moderate/severe PD development; and 3) switching to a STD diet does not halt/reverse PD that was accelerated by an H-SC diet. These data further clarify use of the rice rat as a PD model.
| S-EPMC5539967 | biostudies-other
Project description:The mechanisms underlying the crosstalk between periodontitis and osteoporosis remain unclear. Recently, the gut microbiota has been recognized as a pivotal regulator of bone metabolism, and oral and gut mucosae are microbiologically connected. In this study, we investigated the effects of periodontitis on osteoporosis through the oral-gut axis. The salivary microbiota of patients with periodontitis was collected and then pumped into the intestine of Sprague-Dawley rats via intragastric administration for 2 weeks. An osteoporosis model was established using ovariectomy. Changes in the maxillae and femora were evaluated using microcomputed tomography (micro CT) and HE staining. Intestinal barrier integrity and inflammatory factors were examined using real-time quantitative polymerase chain reaction and immunofluorescence. The gut microbiota was profiled by 16S rRNA gene sequencing. Metabolome profiling of serum was performed using liquid chromatography-mass spectrometry sequencing. Micro CT and HE staining revealed osteoporotic phenotypes in the maxillae and femora of ovariectomized (OVX) rats. Our results confirmed that the salivary microbiota of patients with periodontitis aggravated femoral bone resorption in OVX rats. In addition, intestinal inflammation was exacerbated after periodontitis salivary microbiota gavage in OVX rats. Correlation analysis of microbiota and metabolomics revealed that lipolysis and tryptophan metabolism may be related to the bone loss induced by the salivary microbiota of patients with periodontitis. In conclusion, periodontitis can aggravate long bone loss through the oral-gut axis in OVX rats.
| S-EPMC9411930 | biostudies-literature
Project description:AimThe objective of this research was to perform a pilot study to develop an automatic analysis of periapical radiographs from patients with and without periodontitis for the percentage alveolar bone loss (ABL) on the approximal surfaces of teeth using a supervised machine learning model, that is, convolutional neural networks (CNN).Material and methodsA total of 1546 approximal sites from 54 participants on mandibular periapical radiographs were manually annotated (MA) for a training set (n = 1308 sites), a validation set (n = 98 sites), and a test set (n = 140 sites). The training and validation sets were used for the development of a CNN algorithm. The algorithm recognised the cemento-enamel junction, the most apical extent of the alveolar crest, the apex, and the surrounding alveolar bone.ResultsFor the total of 140 images in the test set, the CNN scored a mean of 23.1 ± 11.8 %ABL, whilst the corresponding value for MA was 27.8 ± 13.8 %ABL. The intraclass correlation (ICC) was 0.601 (P < .001), indicating moderate reliability. Further subanalyses for various tooth types and various bone loss patterns showed that ICCs remained significant, although the algorithm performed with excellent reliability for %ABL on nonmolar teeth (incisors, canines, premolars; ICC = 0.763).ConclusionsA CNN trained algorithm on radiographic images showed a diagnostic performance with moderate to good reliability to detect and quantify %ABL in periapical radiographs.
| S-EPMC9485533 | biostudies-literature
Project description:Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-? secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro-computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis-induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-? ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.
| S-EPMC6761736 | biostudies-literature
Project description:Periodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1?, IL-6, TNF-? and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36?/IL-36?/IL-36?/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. We showed here that IL-36? mRNA gingival expression is higher in periodontitis patients, whereas IL-36? and IL-36Ra mRNA expression are lower compared to healthy controls. Interestingly, the elevated IL-36? expression in patients is positively correlated with the RANKL/OPG ratio, an index of bone resorption. In vitro, IL-36? expression was induced through TLR2 activation in primary OECs infected with P. gingivalis but not in gingival fibroblasts, the most widespread cell type in gingival connective tissue. In OECs, recombinant IL-36? enhanced the expression of inflammatory cytokines (IL-1?, IL-6, TNF-? and IL-36?), of TLR2 and importantly, the RANKL/OPG ratio. These findings suggest that IL-36? could be a pivotal inflammatory player in periodontitis by perpetuating gingival inflammation and its associated alveolar bone resorption and could be a relevant therapeutic target.
| S-EPMC6917751 | biostudies-literature
Project description:Periodontitis is an inflammatory disease caused by microorganisms that induce the destruction of periodontal tissue. Inflamed and damaged tissue produces various inflammatory cytokines, which activate osteoclasts and induce alveolar bone loss and, eventually, tooth loss. Sirt6 expression suppresses inflammation and bone resorption; however, its role in periodontitis remains unclear. We hypothesized that Sirt6 has a protective role in periodontitis. To understand the role of Sirt6 in periodontitis, we compared periodontitis with ligature placement around the maxillary left second molar in 8-week-old control (C57BL/6J) male mice to Sirt6-overexpressing Tg (Sirt6Tg) mice, and we observed the resulting phenotypes using micro-CT. MDL801, a Sirt6 activator, was used as a therapy for periodontitis through oral gavage. Pro-inflammatory cytokines and increased osteoclast numbers were observed in alveolar bone tissue under periodontitis surgery. In the same condition, interestingly, protein levels from Sirt6 were the most downregulated among sirtuins in alveolar bone tissue. Based on micro-CT and CEJ-ABC distance, Sirt6Tg was observed to resist bone loss against ligature-induced periodontitis. Furthermore, the number of osteoclasts was significantly reduced in Sirt6Tg-ligated mice compared with control-ligated mice, although systemic inflammatory cytokines did not change. Consistent with this observation, we confirmed that bone loss was significantly reduced when MDL801, a Sirt6 activator, was included in the ligation mouse model. Our findings demonstrate that Sirt6 activation prevents bone loss against ligature-induced periodontitis. Thus, a Sirt6 activator may provide a new therapeutic approach for periodontitis.
| S-EPMC10341680 | biostudies-literature
Project description:Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss. With the progression of periodontitis, the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption. CD301b+ macrophages are specific to the osteoimmunology microenvironment, and are emerging as vital booster for conducting bone regeneration. However, the key upstream targets of CD301b+ macrophages and their potential mechanism in periodontitis remain elusive. In this study, we concentrated on the role of Tim4, a latent upstream regulator of CD301b+ macrophages. We first demonstrated that the transcription level of Timd4 (gene name of Tim4) in CD301b+ macrophages was significantly upregulated compared to CD301b- macrophages via high-throughput RNA sequencing. Moreover, several Tim4-related functions such as apoptotic cell clearance, phagocytosis and engulfment were positively regulated by CD301b+ macrophages. The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages. The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+ macrophages as periodontitis progressed. Furthermore, the deficiency of Tim4 in mice decreased CD301b+ macrophages and eventually magnified alveolar bone resorption in periodontitis. Additionally, Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+ macrophages phenotype. In a word, Tim4 might regulate CD301b+ macrophages through p38 MAPK signaling pathway in periodontitis, which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.
| S-EPMC10902347 | biostudies-literature