scholarly journals Gut-Bone Axis: A Non-Negligible Contributor to Periodontitis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyue Jia ◽  
Ran Yang ◽  
Jiyao Li ◽  
Lei Zhao ◽  
Xuedong Zhou ◽  
...  
Keyword(s):  
Bone Loss ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Bone Health ◽  
Alveolar Bone ◽  
Systemic Diseases ◽  
Bone Homeostasis ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms ◽  
Gut Pathogens

Periodontitis is a polymicrobial infectious disease characterized by alveolar bone loss. Systemic diseases or local infections, such as diabetes, postmenopausal osteoporosis, obesity, and inflammatory bowel disease, promote the development and progression of periodontitis. Accumulating evidences have revealed the pivotal effects of gut microbiota on bone health via gut-alveolar-bone axis. Gut pathogens or metabolites may translocate to distant alveolar bone via circulation and regulate bone homeostasis. In addition, gut pathogens can induce aberrant gut immune responses and subsequent homing of immunocytes to distant organs, contributing to pathological bone loss. Gut microbial translocation also enhances systemic inflammation and induces trained myelopoiesis in the bone marrow, which potentially aggravates periodontitis. Furthermore, gut microbiota possibly affects bone health via regulating the production of hormone or hormone-like substances. In this review, we discussed the links between gut microbiota and periodontitis, with a particular focus on the underlying mechanisms of gut-bone axis by which systemic diseases or local infections contribute to the pathogenesis of periodontitis.

scholarly journals An emerging role of Prevotella histicola on estrogen-deficiency induced bone loss through the gut microbiota-bone axis

2020 ◽  
Author(s):  
Zhongxiang Wang ◽  
Kai Chen ◽  
Congcong Wu ◽  
Junhao Chen ◽  
Hao Pan ◽  
...  
Keyword(s):  
Bone Loss ◽  
Gut Microbiota ◽  
Bone Mass ◽  
16S Rrna Gene Sequencing ◽  
Estrogen Deficiency ◽  
Rrna Gene ◽  
Protective Effects ◽  
Bone Homeostasis ◽  
Rrna Gene Sequencing ◽  
Underlying Mechanisms

AbstractGut microbiota (GM)-bone axis has emerged as a crucial mediator in the maintenance of bone homeostasis. Estrogen-deficiency induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain not fully understood. To this end, feces samples collected from the postmenopausal patients with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16s rRNA gene sequencing. We found that GM in PMO group was featured by a significant decreased proportion of genus Prevotella in comparison with that in the PMN group. Next, Prevotella histicola (P.histicola), a typical specie of Prevotella, was orally given to the mice following the ovariectomy (OVX) procedure and it significantly prevented OVX induced bone loss. Mechanistically, the protective effects of P.histicola on bone mass were found to be associated with the inhibition of osteoclastic resorption by attenuating osteoclastogenic cytokines expression and ameliorating gut permeability. Thus, P.histicola may prevent estrogen-deficiency induced bone loss through the GM-bone axis.

scholarly journals Probiotics ameliorate alveolar bone loss by regulating gut microbiota

2021 ◽  
Author(s):  
Leming Jia ◽  
Ye Tu ◽  
Xiaoyue Jia ◽  
Qian Du ◽  
Xin Zheng ◽  
...  
Keyword(s):  
Bone Loss ◽  
Gut Microbiota ◽  
Alveolar Bone ◽  
Alveolar Bone Loss

scholarly journals miR-542-3p Attenuates Bone Loss and Marrow Adiposity Following Methotrexate Treatment by Targeting sFRP-1 and Smurf2

2021 ◽  
Vol 22 (20) ◽  
pp. 10988
Author(s):  
Ya-Li Zhang ◽  
Liang Liu ◽  
Yu-Wen Su ◽  
Cory J. Xian
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Target Prediction ◽  
In Vitro Models ◽  
Bone Homeostasis ◽  
Marrow Fat ◽  
Childhood Malignancies ◽  
Marrow Adiposity ◽  
Underlying Mechanisms

Intensive methotrexate (MTX) treatment for childhood malignancies decreases osteogenesis but increases adipogenesis from the bone marrow stromal cells (BMSCs), resulting in bone loss and bone marrow adiposity. However, the underlying mechanisms are unclear. While microRNAs (miRNAs) have emerged as bone homeostasis regulators and miR-542-3p was recently shown to regulate osteogenesis in a bone loss context, the role of miR-542-3p in regulating osteogenesis and adipogenesis balance is not clear. Herein, in a rat MTX treatment-induced bone loss model, miR-542-3p was found significantly downregulated during the period of bone loss and marrow adiposity. Following target prediction, network construction, and functional annotation/ enrichment analyses, luciferase assays confirmed sFRP-1 and Smurf2 as the direct targets of miR-542-3p. miRNA-542-3p overexpression suppressed sFRP-1 and Smurf2 expression post-transcriptionally. Using in vitro models, miR-542-3p treatment stimulated osteogenesis but attenuated adipogenesis following MTX treatment. Subsequent signalling analyses revealed that miR-542-3p influences Wnt/β-catenin and TGF-β signalling pathways in osteoblastic cells. Our findings suggest that MTX treatment-induced bone loss and marrow adiposity could be molecularly linked to miR-542-3p pathways. Our results also indicate that miR-542-3p might be a therapeutic target for preserving bone and attenuating marrow fat formation during/after MTX chemotherapy.

scholarly journals The roles of osteocytes in alveolar bone destruction in periodontitis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaofei Huang ◽  
Mengru Xie ◽  
Yanling Xie ◽  
Feng Mei ◽  
Xiaofeng Lu ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Remodeling ◽  
Alveolar Bone ◽  
Bone Cells ◽  
Bone Destruction ◽  
Alveolar Bone Loss ◽  
Receptor Activator ◽  
Local Destruction ◽  
Underlying Mechanisms

AbstractPeriodontitis, a bacterium-induced inflammatory disease that is characterized by alveolar bone loss, is highly prevalent worldwide. Elucidating the underlying mechanisms of alveolar bone loss in periodontitis is crucial for understanding its pathogenesis. Classically, bone cells, such as osteoclasts, osteoblasts and bone marrow stromal cells, are thought to dominate the development of bone destruction in periodontitis. Recently, osteocytes, the cells embedded in the mineral matrix, have gained attention. This review demonstrates the key contributing role of osteocytes in periodontitis, especially in alveolar bone loss. Osteocytes not only initiate physiological bone remodeling but also assist in inflammation-related changes in bone remodeling. The latest evidence suggests that osteocytes are involved in regulating bone anabolism and catabolism in the progression of periodontitis. The altered secretion of receptor activator of NF-κB ligand (RANKL), sclerostin and Dickkopf-related protein 1 (DKK1) by osteocytes affects the balance of bone resorption and formation and promotes bone loss. In addition, the accumulation of prematurely senescent and apoptotic osteocytes observed in alveolar bone may exacerbate local destruction. Based on their communication with the bloodstream, it is noteworthy that osteocytes may participate in the interaction between local periodontitis lesions and systemic diseases. Overall, further investigations of osteocytes may provide vital insights that improve our understanding of the pathophysiology of periodontitis.

scholarly journals Oral Immunization with RecombinantStreptococcus gordonii Expressing Porphyromonas gingivalis FimA Domains

2001 ◽  
Vol 69 (5) ◽  
pp. 2928-2934 ◽  
Author(s):  
Ashu Sharma ◽  
Kiyonobu Honma ◽  
Richard T. Evans ◽  
Dennis E. Hruby ◽  
Robert J. Genco
Keyword(s):  
Bone Loss ◽  
Immune Responses ◽  
Porphyromonas Gingivalis ◽  
Oral Delivery ◽  
Alveolar Bone ◽  
Vaccine Development ◽  
Alveolar Bone Loss ◽  
Biologically Active ◽  
Mucosal Vaccine ◽  
Critical Surface

ABSTRACT Porphyromonas gingivalis, a gram-negative anaerobe, is implicated in the etiology of adult periodontitis. P. gingivalis fimbriae are one of several critical surface virulence factors involved in both bacterial adherence and inflammation. P. gingivalis fimbrillin (FimA), the major subunit protein of fimbriae, is considered an important antigen for vaccine development against P. gingivalis-associated periodontitis. We have previously shown that biologically active domains of P. gingivalis fimbrillin can be expressed on the surface of the human commensal bacterium Streptococcus gordonii. In this study, we examined the effects of oral coimmunization of germfree rats with two S. gordonii recombinants expressing N (residues 55 to 145)- and C (residues 226 to 337)-terminal epitopes of P. gingivalis FimA to elicit FimA-specific immune responses. The effectiveness of immunization in protecting against alveolar bone loss following P. gingivalis infection was also evaluated. The results of this study show that the oral delivery of P. gingivalis FimA epitopes via S. gordonii vectors resulted in the induction of FimA-specific serum (immunoglobulin G [IgG] and IgA) and salivary (IgA) antibody responses and that the immune responses were protective against subsequent P. gingivalis-induced alveolar bone loss. These results support the potential usefulness of the S. gordonii vectors expressingP. gingivalis fimbrillin as a mucosal vaccine against adult periodontitis.

scholarly journals Eosinophilia is induced in the colon of Th2-sensitized mice upon exposure to locally expressed antigen

2007 ◽  
Vol 293 (1) ◽  
pp. G383-G390 ◽  
Author(s):  
Qing Zhu ◽  
Christopher W. Thomson ◽  
Guofeng Zhang ◽  
Martin Stämpfli ◽  
Mark R. McDermott ◽  
...  
Keyword(s):  
Immune Responses ◽  
Colonic Mucosa ◽  
Cell Damage ◽  
Adenovirus Vector ◽  
Eosinophil Infiltration ◽  
Gi Tract ◽  
Colonic Inflammation ◽  
Immediate Function ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Eosinophilic inflammation is a feature of a variety of gastrointestinal (GI) disorders including eosinophil-associated GI disorder, allergy, inflammatory bowel disease, and parasite infection. Elucidating the mechanisms of eosinophil infiltration into the GI tract is important to the understanding of multiple disease processes. We hypothesize that eosinophilia in the large intestine (colon) can be induced by an antigen in a host that is associated with Th2-skewed antigen-specific immune responses. To investigate the importance of antigenic triggering, we established polarized antigen-specific Th2 type responses in BALB/c mice, using ovalbumin in conjunction with aluminum hydroxide. Upon challenge at the colonic mucosa through transient (3–4 days) expression of the antigen gene encoded in an adenovirus vector, sensitized animals developed significant subepithelial colonic inflammation, characterized by marked eosinophilic infiltration, and the presence of enlarged and increased numbers of lymphoid follicles. The alterations peaked around day 5 and resolved over the next 5–10 days, and no epithelial cell damage was detected through the entire course. Administration of a control (empty) adenovirus vector did not lead to any pathological changes. These data suggest that colonic eosinophilia can be induced by exposure to an antigen associated with preexisting Th2-skewed responses. Thus the model established here may provide a useful tool to study GI and, in particular, colonic inflammation with respect to underlying mechanisms involved in the recruitment and the immediate function of eosinophils.

scholarly journals Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Lingyun Lu ◽  
Mengjia Tang ◽  
Jiao Li ◽  
Ying Xie ◽  
Yujue Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Bone Loss ◽  
Gut Microbiota ◽  
Enzyme Linked Immunosorbent Assay ◽  
Bone Homeostasis ◽  
High Fat ◽  
Serum Metabolites ◽  
Bone Marrow Adipose Tissue ◽  
Marrow Adipose Tissue

BackgroundAccumulating evidence indicates that high-fat diet (HFD) is a controllable risk factor for osteoporosis, but the underlying mechanism remains to be elucidated. As a primary biological barrier for nutrient entry into the human body, the composition and function of gut microbiota (GM) can be altered rapidly by HFD, which may trigger abnormal bone metabolism. In the current study, we analyzed the signatures of GM and serum metabolomics in HFD-induced bone loss and explored the potential correlations of GM and serum metabolites on HFD-related bone loss.MethodsWe conducted a mouse model with HFD-induced bone loss through a 12-week diet intervention. Micro-CT, Osmium-μCT, and histological analyses were used to observe bone microstructure and bone marrow adipose tissue. Quantitative Real-Time PCR was applied to analyze gene expression related to osteogenesis, adipogenesis, and osteoclastogenesis. Enzyme-linked immunosorbent assay was used to measure the biochemical markers of bone turnover. 16s rDNA sequencing was employed to analyze the abundance of GM, and UHPLC-MS/MS was used to identify serum metabolites. Correlation analysis was performed to explore the relationships among bone phenotypes, GM, and the metabolome.ResultsHFD induced bone loss accompanied by bone marrow adipose tissue expansion and bone formation inhibition. In the HFD group, the relative abundance of Firmicutes was increased significantly, while Bacteroidetes, Actinobacteria, Epsilonbacteraeota, and Patescibacteria were decreased compared with the ND group. Association analysis showed that thirty-two bacterial genera were significantly related to bone volume per tissue volume (BV/TV). One hundred and forty-five serum metabolites were identified as differential metabolites associated with HFD intervention, which were significantly enriched in five pathways, such as purine metabolism, regulation of lipolysis in adipocyte and cGMP-PKG signaling pathway. Sixty-four diffiential metabolites were matched to the MS2 spectra; and ten of them were positively correlated with BV/TV and five were negatively correlated with BV/TV.ConclusionsThese findings indicated that the alternations of GM and serum metabolites were related to HFD-induced bone loss, which might provide new insights into explain the occurrence and development of HFD-related osteoporosis. The regulatory effects of GM and metabolites associated with HFD on bone homeostasis required further exploration.

γδ T Cells Differentially Regulate Bone Loss in Periodontitis Models

2021 ◽  
pp. 002203452110428
Author(s):  
O. Barel ◽  
Y. Aizenbud ◽  
Y. Tabib ◽  
Y. Jaber ◽  
A. Leibovich ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Bone Loss ◽  
Immune Responses ◽  
Alveolar Bone ◽  
Γδ T Cells ◽  
Oral Infection ◽  
Alveolar Bone Loss ◽  
Infection Model ◽  
The Impact

γδ T cells are nonclassical T lymphocytes representing the major T-cell population at epithelial barriers. In the gingiva, γδ T cells are enriched in epithelial regions adjacent to the biofilm and are considered to regulate local immunity to maintain host-biofilm homeostatic interactions. This delicate balance is often disrupted resulting in the development of periodontitis. Previous studies in mice lacking γδ T cells from birth ( Tcrd-/- mice) examined the impact of these cells on ligature-induced periodontitis. Data obtained from those studies proposed either a protective effect or no impact to γδ T cells in this setting. Here, we addressed the role of γδ T cells in periodontitis using the recently developed Tcrd-GDL mice, enabling temporal ablation of γδ T cells. Specifically, the impact of γδ T cells during periodontitis was examined in 2 modalities: the ligature model and the oral infection model in which the pathogen Porphyromonas gingivalis was administrated via successive oral gavages. Ablation of γδ T cells during ligature-induced periodontitis had no impact on innate immune cell recruitment to the ligated gingiva. In addition, the number of osteoclasts and subsequent alveolar bone loss were unaffected. However, γδ T cells play a pathologic role during P. gingivalis infection, and their absence prevented alveolar bone loss. Further analysis revealed that γδ T cells were responsible for the recruitment of neutrophils and monocytes to the gingiva following the exposure to P. gingivalis. γδ T-cell ablation also downregulated osteoclastogenesis and dysregulated long-term immune responses in the gingiva. Collectively, this study demonstrates that whereas γδ T cells are dispensable to periodontitis induced by the ligature model, they play a deleterious role in the oral infection model by facilitating pathogen-induced bone-destructive immune responses. On a broader aspect, this study highlights the complex immunopathologic mechanisms involved in periodontal bone loss.

Diet-induced obesity, gut microbiota and bone, including alveolar bone loss

2017 ◽  
Vol 78 ◽  
pp. 65-81 ◽  
Author(s):  
Sathima Eaimworawuthikul ◽  
Parameth Thiennimitr ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Bone Loss ◽  
Gut Microbiota ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Diet Induced Obesity

scholarly journals Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota

2018 ◽  
Vol 98 (1) ◽  
pp. 107-116 ◽  
Author(s):  
X. Jia ◽  
L. Jia ◽  
L. Mo ◽  
S. Yuan ◽  
X. Zheng ◽  
...  
Keyword(s):  
Bone Loss ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Alveolar Bone ◽  
Intestinal Barrier ◽  
Alveolar Bone Loss ◽  
Micro Computed Tomography ◽  
Ovx Rats ◽  
Obesity And Diabetes ◽  
Periodontal Bone Loss

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro–computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency–aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

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