scholarly journals PTEN Inhibits Inflammatory Bone Loss in Ligature-Induced Periodontitis via IL1 and TNF-α

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chuanyun Fu ◽  
Zhimin Wei ◽  
Dongsheng Zhang
Keyword(s):  
Bone Remodeling ◽  
Alveolar Bone ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Inflammatory Factors ◽  
Oral Diseases ◽  
Periodontal Tissues ◽  
Tensin Homolog ◽  
Key Factor

Phosphatase and tensin homolog (PTEN) is a critical regulator of tumorigenesis and bone remodeling, which is also found expressed in the periodontal tissues. Periodontitis is one of the most common oral diseases and associated with alveolar bone resorption and tooth loosening in adults. However, the functional relevance of PTEN in periodontitis remains unclear. Here, we report that PTEN plays an essential role in periodontitis. The in vivo results of our study showed a significant decrease of PTEN in the ligature-induced mouse periodontitis model. The function of PTEN in the macrophages was shown to be associated with inflammatory factors interleukin 1 (IL1) and tumor necrosis factor (TNF-α) by using overexpression and silence methods. Further mechanistic studies indicated lack of PTEN-activated IL1 and TNF-α, which increased the number of osteoclasts and led to alveolar bone erosion and loss. Moreover, PTEN nanoparticles could directly inhibit the inflammatory process and bone erosion, suggesting a controlling role of PTEN during bone remodeling. All these data identified the novel function of PTEN as a key factor in periodontitis and bone remodeling.

Orthodontic Force–Induced BMAL1 in PDLCs Is a Vital Osteoclastic Activator

2021 ◽  
pp. 002203452110199
Author(s):  
Y. Xie ◽  
Q. Tang ◽  
S. Yu ◽  
W. Zheng ◽  
G. Chen ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Nuclear Factor Κb ◽  
Periodontal Ligament Cells ◽  
Orthodontic Force ◽  
Periodontal Tissues ◽  
Alveolar Bone Remodeling ◽  
Biomechanical Stimuli

Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs) sensing biomechanical stimuli and subsequently releasing signals to initiate alveolar bone remodeling. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities are still unclear. This study demonstrates that the core circadian protein aryl hydrocarbon receptor nuclear translocator–like protein 1 (BMAL1) in PDLCs is highly involved in sensing and delivering biomechanical signals. Orthodontic force upregulates BMAL1 expression in periodontal tissues and cultured PDLCs in manners dependent on ERK (extracellular signal–regulated kinase) and AP1 (activator protein 1). Increased BMAL1 expression can enhance secretion of CCL2 (C-C motif chemokine 2) and RANKL (receptor activator of nuclear factor–κB ligand) in PDLCs, which subsequently promotes the recruitment of monocytes that differentiate into osteoclasts. The mechanistic delineation clarifies that AP1 induced by orthodontic force can directly interact with the BMAL1 promoter and activate gene transcription in PDLCs. Localized administration of the ERK phosphorylation inhibitor U0126 or the BMAL1 inhibitor GSK4112 suppressed ERK/AP1/BMAL1 signaling. These treatments dramatically reduced osteoclastic activity in the compression side of a rat orthodontic model, and the OTM rate was almost nonexistent. In summary, our results suggest that force-induced expression of BMAL1 in PDLCs is closely involved in controlling osteoclastic activities during OTM and plays a vital role in alveolar bone remodeling. It could be a useful therapeutic target for accelerating the OTM rate and controlling pathologic bone-remodeling activities.

scholarly journals The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Qing Lv ◽  
Qinghua Xia ◽  
Anshu Li ◽  
Zhiyong Wang
Keyword(s):  
Tumor Microenvironment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Stomach Carcinoma ◽  
Downstream Target ◽  
Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

scholarly journals The potentiation of Mangifera casturi bark extract on interleukin- 1β and bone morphogenic protein-2 expressions during bone remodeling after tooth extraction

2017 ◽  
Vol 50 (1) ◽  
pp. 36
Author(s):  
Bayu Indra Sukmana ◽  
Theresia Indah Budhy ◽  
I Gusti Aju Wahju Ardani
Keyword(s):  
Bone Remodeling ◽  
Tooth Extraction ◽  
Alveolar Bone ◽  
Interleukin 1 ◽  
Bone Morphogenic Protein ◽  
Bark Extract ◽  
Control Group ◽  
Tooth Decay ◽  
Significant Difference ◽  
Bone Morphogenic Protein 2

Background: The main oral health problem in Indonesia is the high number of tooth decay. Tooth extraction is the treatment often received by patients who experience tooth decay and the wound caused by alveolar bone resorption. Bark of Mangifera casturi has been studied and proven to contain secondary metabolite which has the ability to increase osteoblast’s activity and suppress osteoclast’s activity. Purpose: The purpose of this study was to analyze interleukin-1 beta (IL-1β) and bone morphogenic protein-2 (BMP-2) activities during bone remodeling after Mangifera casturi’s bark extract treatment. Method: This study was laboratory experimental research with randomized post-test only control group design. The Mangifera casturi bark was extracted using 96% ethanol maceration and n-hexane fractionation. This study used 40 male Wistar rats which are divided into 4 groups and the tooth extraction was performed on the rats’ right mandible incisive tooth. The four groups consisted of 6.35%, 12.7%, 25.4% extract treatment group, and a control group. Wistar’s mandibles were decapitated on the 7th and 14th day after extraction. Antibody staining on preparations for the examination of IL-1β and BMP-2 expressions was done using immunohistochemistry. Result: There was a significant difference of IL-1β and BMP-2 expressions in 6,35%, 12,7%, and 25,4% treatment groups compared to control group with p<0.05. Conclusion: Mangifera casturi’s bark extract was able to suppress the IL-1β expression and increase the BMP-2 expression during bone remodeling after tooth extraction.

scholarly journals A New Polycaprolactone-Based Biomembrane Functionalized with BMP-2 and Stem Cells Improves Maxillary Bone Regeneration

Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1774
Author(s):  
Céline Stutz ◽  
Marion Strub ◽  
François Clauss ◽  
Olivier Huck ◽  
Georg Schulz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Remodeling ◽  
New Technology ◽  
Bone Lesion ◽  
Oral Diseases ◽  
Maxillary Bone

Oral diseases have an impact on the general condition and quality of life of patients. After a dento-alveolar trauma, a tooth extraction, or, in the case of some genetic skeletal diseases, a maxillary bone defect, can be observed, leading to the impossibility of placing a dental implant for the restoration of masticatory function. Recently, bone neoformation was demonstrated after in vivo implantation of polycaprolactone (PCL) biomembranes functionalized with bone morphogenic protein 2 (BMP-2) and ibuprofen in a mouse maxillary bone lesion. In the present study, human bone marrow derived mesenchymal stem cells (hBM-MSCs) were added on BMP-2 functionalized PCL biomembranes and implanted in a maxillary bone lesion. Viability of hBM-MSCs on the biomembranes has been observed using the “LIVE/DEAD” viability test and scanning electron microscopy (SEM). Maxillary bone regeneration was observed for periods ranging from 90 to 150 days after implantation. Various imaging methods (histology, micro-CT) have demonstrated bone remodeling and filling of the lesion by neoformed bone tissue. The presence of mesenchymal stem cells and BMP-2 allows the acceleration of the bone remodeling process. These results are encouraging for the effectiveness and the clinical use of this new technology combining growth factors and mesenchymal stem cells derived from bone marrow in a bioresorbable membrane.

scholarly journals Knockdown adiponectin receptor 1 expression in synovial tissue alleviate the progression of collagen-induced arthritis

2019 ◽  
Author(s):  
Yani Wang ◽  
Rui Liu ◽  
Pengfei Zhao ◽  
Qian Zhang ◽  
Yingheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Bone Erosion ◽  
Adiponectin Receptor ◽  
Inflammatory Factors ◽  
Nuclear Factor ◽  
Collagen Induced Arthritis ◽  
Adiponectin Receptor 1 ◽  
Receptor Activator

Abstract Background: Previous studies have shown that adiponectin (APN) is involved in the pathogenesis of rheumatoid arthritis (RA). The proinflammatory effect of APN is mainly mediated adiponectin receptor 1 (AdipoR1). The high expression of AdipoR1 have been suggested in RA synovial tissue. This study was aimed to investigate the effects of AdipoR1 in inflammation and bone erosion in collagen-induced arthritis (CIA) mice, and to further explore the underlying mechanisms. Methods: The expression of APN and AdipoR1 in synovial tissue of RA and osteoarthritis (OA) patient was tested by qPCR and western blot. RA synovial fibroblasts (RASFs) were stimulated with APN, IL-6 or TNF-α respectively. The expression of AdipoR1 on RASFs were tested by flow cytometry. To prove the pathogenic role, AdipoR1 was silenced in a human rheumatoid arthritis synovial fibroblast cell line (MH7A) and local joint of CIA mice by specific short hairpin RNAs (shRNAs) using a lentiviral delivery system. The levels of proliferation, apoptosis and inflammatory factors on MH7A were assessed in vitro. Local AdipoR1 knockdown on CIA mice were further estimated by arthritis clinical scores, inflammatory cytokine expression, micro-CT, H&E staining and receptor activator of nuclear factor к B ligand (RANKL) / osteoprotegerin (OPG) in vivo. Results: We found that the levels of APN and AdipoR1 expression were significantly higher in RASFs and the expression of AdipoR1 was upregulated by APN in RASFs. Silencing AdipoR1 could effectively reduce lipopolysaccharides (LPS) induced proliferation of MH7A cells, promote their apoptosis, and reduce the release of inflammatory factors. In CIA mice, local silencing AdipoR1 in arthritis markedly reduced joint inflammation and alleviated bone erosion and osteoporosis in vivo. Furthermore, local silencing AdipoR1 inhibited receptor activator of nuclear factor к B ligand (RANKL) expression and decreased RANKL / osteoprotegerin (OPG) ratio in knees and ankles of CIA mice. Conclusions: This study suggests that AdipoR1 plays a key role in the development of RA and silencing AdipoR1 might be a new target for the clinical treatment of RA.

scholarly journals Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement

2021 ◽  
Vol 12 ◽  
Author(s):  
Yukun Jiang ◽  
Yuzhe Guan ◽  
Yuanchen Lan ◽  
Shuo Chen ◽  
Tiancheng Li ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Critical Role ◽  
Orthodontic Tooth Movement ◽  
Chemical Signals ◽  
Periodontal Tissues ◽  
Alveolar Bone Remodeling ◽  
Pdl Cells

Orthodontic tooth movement (OTM) is a process depending on the remodeling of periodontal tissues surrounding the roots. Orthodontic forces trigger the conversion of mechanical stimuli into intercellular chemical signals within periodontal ligament (PDL) cells, activating alveolar bone remodeling, and thereby, initiating OTM. Recently, the mechanosensitive ion channel Piezo1 has been found to play pivotal roles in the different types of human cells by transforming external physical stimuli into intercellular chemical signals. However, the function of Piezo1 during the mechanotransduction process of PDL cells has rarely been reported. Herein, we established a rat OTM model to study the potential role of Piezo1 during the mechanotransduction process of PDL cells and investigate its effects on the tension side of alveolar bone remodeling. A total of 60 male Sprague-Dawley rats were randomly assigned into three groups: the OTM + inhibitor (INH) group, the OTM group, and the control (CON) group. Nickel-titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on days 0, 3, 7, and 14 after orthodontic movement for the radiographic, histological, immunohistochemical, and molecular biological analyses. Our results revealed that the Piezo1 channel was activated by orthodontic force and mainly expressed in the PDL cells during the whole tooth movement period. The activation of the Piezo1 channel was essential for maintaining the rate of orthodontic tooth movement and facilitation of new alveolar bone formation on the tension side. Reduced osteogenesis-associated transcription factors such as Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio were examined when the function of Piezo1 was inhibited. In summary, Piezo1 plays a critical role in mediating both the osteogenesis and osteoclastic activities on the tension side during OTM.

scholarly journals Interspecies Comparison of Alveolar Bone Biology, Part I: Morphology and Physiology of Pristine Bone

2020 ◽  
pp. 238008442093697
Author(s):  
I. Pilawski ◽  
U.S. Tulu ◽  
P. Ticha ◽  
P. Schüpbach ◽  
H. Traxler ◽  
...  
Keyword(s):  
Animal Models ◽  
Bone Remodeling ◽  
Alveolar Bone ◽  
State Of The Art ◽  
Tartrate Resistant Acid Phosphatase ◽  
Knowledge Gap ◽  
Bone Biology ◽  
Mineral Density ◽  
Surgical Interventions

Introduction: Few interspecies comparisons of alveolar bone have been documented, and this knowledge gap raises questions about which animal models most accurately represent human dental conditions or responses to surgical interventions. Objectives: The objective of this study was to employ state-of-the-art quantitative metrics to directly assess and compare the structural and functional characteristics of alveolar bone among humans, mini pigs, rats, and mice. Methods: The same anatomic location (i.e., the posterior maxillae) was analyzed in all species via micro–computed tomographic imaging, followed by quantitative analyses, coupled with histology and immunohistochemistry. Bone remodeling was evaluated with alkaline phosphatase activity and tartrate-resistant acid phosphatase staining to identify osteoblast and osteoclast activities. In vivo fluorochrome labeling was used as a means to assess mineral apposition rates. Results: Collectively, these analyses demonstrated that bone volume differed among the species, while bone mineral density was equal. All species showed a similar density of alveolar osteocytes, with a highly conserved pattern of collagen organization. Collagen maturation was equal among mouse, rat, and mini pig. Bone remodeling was a shared feature among the species, with morphologically indistinguishable hemiosteonal appearances, osteocytic perilacunar remodeling, and similar mineral apposition rates in alveolar bone. Conclusions: Our analyses demonstrated equivalencies among the 4 species in a plurality of the biological features of alveolar bone. Despite contradictory results from older studies, we found no evidence for the superiority of pig models over rodent models in representing human bone biology. Knowledge Transfer Statement: Animal models are extensively used to evaluate bone tissue engineering strategies, yet there are few state-of-the-art studies that rigorously compare and quantify the factors influencing selection of a given animal model. Consequently, there is an urgent need to assess preclinical animal models for their predictive value to dental research. Our article addresses this knowledge gap and, in doing so, provides a foundation for more effective standardization among animal models commonly used in dentistry.

scholarly journals Gamma Interferon (IFN-γ) and IFN-γ-Inducing Cytokines Interleukin-12 (IL-12) and IL-18 Do Not Augment Infection-Stimulated Bone Resorption In Vivo

2004 ◽  
Vol 11 (1) ◽  
pp. 106-110 ◽  
Author(s):  
Hajime Sasaki ◽  
Khaled Balto ◽  
Nobuyuki Kawashima ◽  
Jean Eastcott ◽  
Katsuaki Hoshino ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Alveolar Bone ◽  
Interleukin 1 ◽  
Bone Destruction ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-γ) and IFN-γ-inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12−/−, IL-18−/−, and IFN-γ−/− mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12−/−, IL-18−/−, and IFN-γ−/− mice had similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-γ−/− mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1α levels. Recombinant IL-12, IL-18, and IFN-γ individually failed to consistently modulate macrophage IL-1α production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN-γ do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways.

scholarly journals Association between Postmenopausal Osteoporosis and Experimental Periodontitis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kai Luo ◽  
Souzhi Ma ◽  
Jianbin Guo ◽  
Yongling Huang ◽  
Fuhua Yan ◽  
...  
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Alveolar Bone ◽  
Ovariectomized Rats ◽  
Whole Body ◽  
Inflammatory Factors ◽  
Mineral Density ◽  
Metabolic Markers ◽  
Periodontal Tissues ◽  
Experimental Periodontitis ◽  
Turnover Markers

To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues.

scholarly journals Inhibition of Rheumatoid Arthritis Using Bark, Leaf, and Male Flower Extracts of Eucommia ulmoides

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yun-Yun Xing ◽  
Jian-Ying Wang ◽  
Kai Wang ◽  
Yan Zhang ◽  
Kun Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Male Flower ◽  
Joint Inflammation ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Eucommia Ulmoides

Eucommia ulmoides Oliv., a native Chinese plant species, has been used as a traditional Chinese medicine formulation to treat rheumatoid arthritis (RA), strengthen bones and muscles, and lower blood pressure. Various parts of this plant such as the bark, leaves, and flowers have been found to have anti-inflammatory properties. E. ulmoides has potential applications as a therapeutic agent against bone disorders, which were investigated in this study. In vitro, RA joint fibroblast-like synoviocytes (RA-FLS) were treated with different concentrations (0, 25, 50, 100, 200, 400, 800, and 1000 μg/mL) of E. ulmoides bark, leaf, and male flower alcoholic extracts (EB, EL, and EF, respectively) to determine their potential cytotoxicity. Tumor necrosis factor- (TNF-) α and nitric oxide (NO) levels in RA-FLS were quantified using enzyme-linked immunosorbent assay (ELISA). Furthermore, collagen-induced arthritis (CIA) rats were treated with EB, EL, EF, Tripterygium wilfordii polyglycoside (TG) or the normal control (Nor), and then ankle joint pathology, bone morphology, and serum and spleen inflammatory cytokine levels were evaluated. The results showed that, in RA-FLS, EB, EL, and EF were not cytotoxic; EB and EF reduced TNF-α supernatant levels; and EB, EL, and EF reduced NO levels. The results of in vivo experiments showed that EB, EL, and EF alleviated ankle swelling and joint inflammation, while all extracts diminished inflammatory cell infiltration, pannus and bone destruction, and bone erosion. All tested extracts inhibited interleukin- (IL-) 6, IL-17, and TNF-α mRNA in the spleen of CIA rats, while EB most effectively reduced osteoclasts and inhibited bone erosion. EF showed the most obvious inhibition of inflammatory factors and pannus. Thus, EB, EL, and EF may alleviate bone destruction by inhibiting inflammation.

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