Zanthoxylum piperitum reversed alveolar bone loss of periodontitis via regulation of bone remodeling-related factors

Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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Evaluation of long-term orthodontic tooth movement considering bone remodeling process and in the presence of alveolar bone loss using finite element method

Orthodontic Waves ◽

10.1016/j.odw.2016.09.001 ◽

2016 ◽

Vol 75 (4) ◽

pp. 85-96 ◽

Cited By ~ 4

Author(s):

Azin Zargham ◽

Allahyar Geramy ◽

Gholamreza Rouhi

Keyword(s):

Finite Element Method ◽

Finite Element ◽

Bone Loss ◽

Bone Remodeling ◽

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Alveolar Bone Loss ◽

Element Method

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The roles of osteocytes in alveolar bone destruction in periodontitis

Journal of Translational Medicine ◽

10.1186/s12967-020-02664-7 ◽

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.

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Periodontal status and bone metabolism in women in reproductive and postmenopausal periods

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0011 ◽

2020 ◽

Vol 41 (3) ◽

Author(s):

Iryna Mazur ◽

Bassymbek Dilbarkhanov ◽

Xeniya Kuracha ◽

Volodymyr Novoshytskyy ◽

Iryna Suprunovych ◽

...

Keyword(s):

Bone Loss ◽

Postmenopausal Women ◽

Bone Remodeling ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Postmenopausal Period ◽

Group I ◽

Group Ii

AbstractObjectivesChronic periodontitis is one of the most common diseases in the world. Periodontitis occurs more frequently in postmenopausal women due to hormonal changes and in patients with osteoporosis. Thus, the aim of our study was to compare levels of alveolar bone loss of mandible and maxilla and bone tissue remodeling markers in women of reproductive and postmenopausal periods.MethodsFifty-nine women aged 25–68 years were enrolled in a cross-sectional study and divided into two groups. Group I consisted of 42 women of reproductive age and Group II included 17 women in their postmenopausal period. The level of alveolar bone loss of mandible and maxilla was assessed using dental panoramic radiography, and the level of bone remodeling markers (Beta C-terminal telopeptide of type I collagen [β-CTx] and osteocalcin) was obtained in both groups.ResultsWomen in the postmenopausal period have higher level of alveolar bone loss in mandible and maxilla than women of reproductive age. The level of ß-CTx and osteocalcin was significantly higher in Group II, compared to Group I (p=0.002 and p=0.005, respectively).ConclusionsIn postmenopausal women, on the background of significantly higher bone remodeling, an increase of alveolar bone loss of mandible and maxilla was observed.

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Downregulation of Macrophage-Specific Act-1 Intensifies Periodontitis and Alveolar Bone Loss Possibly via TNF/NF-κB Signaling

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.628139 ◽

2021 ◽

Vol 9 ◽

Author(s):

Janak L. Pathak ◽

Ying Fang ◽

Yunxin Chen ◽

Zhitong Ye ◽

Xueqi Guo ◽

...

Keyword(s):

Bone Loss ◽

Inflammatory Cytokines ◽

Alveolar Bone ◽

Macrophage Polarization ◽

Peritoneal Macrophages ◽

Alveolar Bone Loss ◽

Periodontal Tissue ◽

Related Factors ◽

M1 Macrophage

Periodontitis is a chronic inflammatory oral disease that affects almost half of the adult population. NF-κB activator 1 (Act1) is mainly expressed in immune cells, including macrophages, and modulates immune cells’ function to regulate inflammation in inflammatory diseases. Macrophages play a vital role in the pathophysiology of periodontitis. However, the effect of macrophage-specific Act1 on periodontitis has not been investigated yet. This study aims to unravel the role of macrophage-specific Act1 on the pathophysiology of periodontitis. The expression of Act1 in healthy and periodontitis periodontal tissue was confirmed by immunohistochemistry. Macrophage-specific Act1 expression downregulated (anti-Act1) mice were developed by inserting anti-Act1 antisense oligonucleotides after the CD68 promoter of C57BL/6 mice. Ligature-induced periodontitis (LIP) was induced in anti-Act1 mice and wildtype mice. Micro-CT, histology, and TRAP staining analyzed the periodontal tissue status, alveolar bone loss, and osteoclast numbers. Immunohistochemistry, RT-qPCR, and ELISA analyzed the inflammatory cells infiltration, expression of inflammatory cytokines, and M1/M2 macrophage polarization. mRNA sequencing of in vitro bacterial lipopolysaccharide (LPS)-treated peritoneal macrophages analyzed the differentially expressed genes in anti-Act1 mice during inflammation. Anti-Act1 mice showed aggravated periodontitis and alveolar bone loss compared to wildtype. Periodontitis-affected periodontal tissue (PAPT) of anti-Act1 mice showed a higher degree of macrophage infiltration, and M1 macrophage polarization compared to wildtype. Levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα), and macrophage activity-related factors (CCL2, CCL3, and CCL4) were robustly high in PAPT of anti-Act1 mice compared to wildtype. mRNA sequencing and KEGG analysis showed activated TNF/NF-κB signaling in LPS-treated macrophages from anti-Act1 mice. In vitro studies on LPS-treated peritoneal macrophages from anti-act1 mice showed a higher degree of cell migration and expression of inflammatory cytokines, macrophage activity-related factors, M1 macrophage-related factors, and TNF/NF-κB signaling related P-p65 protein. In conclusion, downregulation of macrophage-specific Act1 aggravated periodontitis, alveolar bone loss, macrophage infiltration, inflammation, and M1 macrophage polarization. Furthermore, LPS-treated macrophages from anti-Act1 mice activated TNF/NF-κB signaling. These results indicate the distinct role of macrophage-specific Act1 on the pathophysiology of periodontitis possibly via TNF/NF-κB signaling.

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EFFECTS OF ALENDRONATE THERAPY ON CYCLOSPORINE INDUCED ALVEOLAR BONE LOSS : A MORPHO-METRIC AND BIO-CHEMICAL STUDY IN RATS

International Journal of Advanced Research ◽

10.21474/ijar01/193 ◽

2016 ◽

Vol 4 (4) ◽

pp. 947-955

Author(s):

Sneha R Bhat ◽

◽

Aravind R Kudva ◽

Dhoom S Mehta ◽

◽

...

Keyword(s):

Bone Loss ◽

Alveolar Bone ◽

Chemical Study ◽

Alveolar Bone Loss

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3,4,5-Trihydroxybenzoic acid attenuates ligature-induced periodontal disease in Wistar rats.

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523019666200206094335 ◽

2020 ◽

Vol 19 ◽

Author(s):

Ozkan Karatas ◽

Fikret Gevrek

Keyword(s):

Bone Loss ◽

Gallic Acid ◽

Wistar Rats ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Collagenase Activity ◽

Osteoblastic Activity ◽

Cell Counts ◽

Experimental Periodontitis ◽

Anti Inflammatory

Background: 3,4,5-Trihydroxybenzoic acid, which is also known as gallic acid, is an anti-inflammatory agent who could provide beneficial effects in preventing periodontal inflammation. The present study aimed to evaluate the anti-inflammatory effects of gallic acid on experimental periodontitis in Wistar rats. Alveolar bone loss, osteoclastic activity, osteoblastic activity, and collagenase activity were also determined. Methods: 32 Wistar rats were used in the present study. Study groups were created as following: Healthy control (C,n=8) group; periodontitis (P,n=8) group; periodontitis and 30 mg/kg gallic acid administered group (G30,n=8); periodontitis and 60 mg/kg gallic acid administered group (G60,n=8). Experimental periodontitis was created by placing 4-0 silk sutures around the mandibular right first molar tooth. Morphological changes in alveolar bone were determined by stereomicroscopic evaluation. Mandibles were undergone histological evaluation. Matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, bone morphogenetic protein (BMP)-2 expressions, tartrate-resistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and inflammatory cell counts were determined. Results: Highest alveolar bone loss was observed in the periodontitis group. Both doses of gallic acid decreased alveolar bone loss compared to the P group. TRAP-positive osteoclast cell counts were higher in the P group, and gallic acid successfully lowered these counts. Osteoblast cells also increased in gallic acid administered groups. Inflammation in the P group was also higher than those of C, G30, and G60 groups supporting the role of gallic acid in preventing inflammation. 30 and 60 mg/kg doses of gallic acid decreased MMP-8 levels and increased TIMP-1 levels. BMP levels increased in gallic acid administered groups, similar to several osteoblasts. Conclusion: Present results revealed an anti-inflammatory effect of gallic acid, which was indicated by decreased alveolar bone loss and collagenase activity and increased osteoblastic activity.

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Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

Scientific Reports ◽

10.1038/s41598-021-92744-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsukasa Tominari ◽

Ayumi Sanada ◽

Ryota Ichimaru ◽

Chiho Matsumoto ◽

Michiko Hirata ◽

...

Keyword(s):

Cell Wall ◽

Bone Loss ◽

Alveolar Bone ◽

Osteoclast Differentiation ◽

Lipoteichoic Acid ◽

Alveolar Bone Loss ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

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