Review for "Different Responsiveness of Alveolar Bone and Long Bone to Epithelial-Mesenchymal Interaction-Related Factor"

AbstractAlveolar bone is the thickened ridge of jaw bone that supports teeth. It is subject to constant occlusal force and pathogens invasion, and is therefore under active bone remodeling and immunomodulation. Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern. However, a systematic explanation of alveolar bone at single-cell level is still lacking. Here, we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing (scRNA-seq). A more active immune microenvironment is identified in alveolar bone, with a higher proportion of mature immune cells than in long bone. Among all immune cell populations, the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells (MSCs) subpopulation. Alveolar bone monocytes/macrophages express a higher level of Oncostatin M (Osm) compared to long bone, which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs. In summary, our study reveals a unique immune microenvironment of alveolar bone, which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.

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Cells Derived from Human Long Bone Appear More Differentiated and More Actively Stimulate Osteoclastogenesis Compared to Alveolar Bone-Derived Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21145072 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5072

Author(s):

Cindy Kelder ◽

Cornelis J. Kleverlaan ◽

Marjolijn Gilijamse ◽

Astrid D. Bakker ◽

Teun J. de Vries

Keyword(s):

Tissue Engineering ◽

Mononuclear Cells ◽

Alveolar Bone ◽

Bone Cells ◽

Transmembrane Protein ◽

Cell Types ◽

Long Bone ◽

Long Bones ◽

Peripheral Blood Mononuclear ◽

Alveolar Bone Cells

Osteoblasts derived from mouse skulls have increased osteoclastogenic potential compared to long bone osteoblasts when stimulated with 1,25(OH)2 vitamin D3 (vitD3). This indicates that bone cells from specific sites can react differently to biochemical signals, e.g., during inflammation or as emitted by bioactive bone tissue-engineering constructs. Given the high turn-over of alveolar bone, we hypothesized that human alveolar bone-derived osteoblasts have an increased osteogenic and osteoclastogenic potential compared to the osteoblasts derived from long bone. The osteogenic and osteoclastogenic capacity of alveolar bone cells and long bone cells were assessed in the presence and absence of osteotropic agent vitD3. Both cell types were studied in osteogenesis experiments, using an osteogenic medium, and in osteoclastogenesis experiments by co-culturing osteoblasts with peripheral blood mononuclear cells (PBMCs). Both osteogenic and osteoclastic markers were measured. At day 0, long bones seem to have a more late-osteoblastic/preosteocyte-like phenotype compared to the alveolar bone cells as shown by slower proliferation, the higher expression of the matrix molecule Osteopontin (OPN) and the osteocyte-enriched cytoskeletal component Actin alpha 1 (ACTA1). This phenotype was maintained during the osteogenesis assays, where long bone-derived cells still expressed more OPN and ACTA1. Under co-culture conditions with PBMCs, long bone cells also had a higher Tumor necrose factor-alfa (TNF-α) expression and induced the formation of osteoclasts more than alveolar bone cells. Correspondingly, the expression of osteoclast genes dendritic cell specific transmembrane protein (DC-STAMP) and Receptor activator of nuclear factor kappa-Β ligand (RankL) was higher in long bone co-cultures. Together, our results indicate that long bone-derived osteoblasts are more active in bone-remodeling processes, especially in osteoclastogenesis, than alveolar bone-derived cells. This indicates that tissue-engineering solutions need to be specifically designed for the site of application, such as defects in long bones vs. the regeneration of alveolar bone after severe periodontitis.

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Dentoalveolar Defects in the Hyp Mouse Model of X-linked Hypophosphatemia

Journal of Dental Research ◽

10.1177/0022034520901719 ◽

2020 ◽

Vol 99 (4) ◽

pp. 419-428 ◽

Cited By ~ 2

Author(s):

H. Zhang ◽

M.B. Chavez ◽

T.N. Kolli ◽

M.H. Tan ◽

H. Fong ◽

...

Keyword(s):

Matrix Protein ◽

Alveolar Bone ◽

Volume Fraction ◽

Fibroblast Growth Factor 23 ◽

Hypophosphatemic Rickets ◽

Long Bone ◽

Micro Ct ◽

Mineral Density ◽

Dentin Matrix Protein ◽

Osteocyte Lacunae

Mutations in PHEX cause X-linked hypophosphatemia (XLH), a form of hypophosphatemic rickets. Hyp ( Phex mutant) mice recapitulate the XLH phenotype. Dental disorders are prevalent in individuals with XLH; however, underlying dentoalveolar defects remain incompletely understood. We analyzed Hyp mouse dentoalveolar defects at 42 and 90 d postnatal to comparatively define effects of XLH on dental formation and function. Phex mRNA was expressed by odontoblasts (dentin), osteocytes (bone), and cementocytes (cellular cementum) in wild-type (WT) mice. Enamel density was unaffected, though enamel volume was significantly reduced in Hyp mice. Dentin defects in Hyp molars were indicated histologically by wide predentin, thin dentin, and extensive interglobular dentin, confirming micro–computed tomography (micro-CT) findings of reduced dentin volume and density. Acellular cementum was thin and showed periodontal ligament detachment. Mechanical testing indicated dramatically altered periodontal mechanical properties in Hyp versus WT mice. Hyp mandibles demonstrated expanded alveolar bone with accumulation of osteoid, and micro-CT confirmed decreased bone volume fraction and alveolar bone density. Cellular cementum area was significantly increased in Hyp versus WT molars owing to accumulation of hypomineralized cementoid. Histology, scanning electron microscopy, and nanoindentation revealed hypomineralized “halos” surrounding Hyp cementocyte and osteocyte lacunae. Three-dimensional micro-CT analyses confirmed larger cementocyte/osteocyte lacunae and significantly reduced perilacunar mineral density. While long bone and alveolar bone osteocytes in Hyp mice overexpressed fibroblast growth factor 23 ( Fgf23), its expression in molars was much lower, with cementocyte Fgf23 expression particularly low. Expression and distribution of other selected markers were disturbed in Hyp versus WT long bone, alveolar bone, and cementum, including osteocyte/cementocyte marker dentin matrix protein 1 ( Dmp1). This study reports for the first time a quantitative analysis of the Hyp mouse dentoalveolar phenotype, including all mineralized tissues. Novel insights into cellular cementum provide evidence for a role for cementocytes in perilacunar mineralization and cementum biology.

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LepR-Expressing Stem Cells Are Essential for Alveolar Bone Regeneration

Journal of Dental Research ◽

10.1177/0022034520932834 ◽

2020 ◽

Vol 99 (11) ◽

pp. 1279-1286 ◽

Cited By ~ 1

Author(s):

D. Zhang ◽

S. Zhang ◽

J. Wang ◽

Q. Li ◽

H. Xue ◽

...

Keyword(s):

Stem Cells ◽

Parathyroid Hormone ◽

Bone Regeneration ◽

Cell Population ◽

Leptin Receptor ◽

Alveolar Bone ◽

Critical Role ◽

Long Bone ◽

Stem Cell Population ◽

Genetic Ablation

Stem cells play a critical role in bone regeneration. Multiple populations of skeletal stem cells have been identified in long bone, while their identity and functions in alveolar bone remain unclear. Here, we identified a quiescent leptin receptor–expressing (LepR+) cell population that contributed to intramembranous bone formation. Interestingly, these LepR+ cells became activated in response to tooth extraction and generated the majority of the newly formed bone in extraction sockets. In addition, genetic ablation of LepR+ cells attenuated extraction socket healing. The parabiosis experiments revealed that the LepR+ cells in the healing sockets were derived from resident tissue rather than peripheral blood circulation. Further studies on the mechanism suggested that these LepR+ cells were responsive to parathyroid hormone/parathyroid hormone 1 receptor (PTH/PTH1R) signaling. Collectively, we demonstrate that LepR+ cells, a postnatal skeletal stem cell population, are essential for alveolar bone regeneration of extraction sockets.

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Probiotics Ameliorate Alveolar Bone Loss by Regulating Gut Microbiota

10.21203/rs.3.rs-97356/v1 ◽

2020 ◽

Author(s):

Leming Jia ◽

Ye Tu ◽

Xiaoyue Jia ◽

Qian Du ◽

Xin Zheng ◽

...

Keyword(s):

Bone Loss ◽

Gut Microbiota ◽

Alveolar Bone ◽

Critical Role ◽

Alveolar Bone Loss ◽

Estrogen Deficiency ◽

Long Bone ◽

Therapeutic Effects ◽

Gut Permeability ◽

Ovx Rats

Abstract BackgroundEstrogen deficiency is an etiological factor of postmenopausal osteoporosis (PMO), which not only decreases bone density in vertebrae and long bone, but also aggravates inflammatory bone loss in alveolar bone. Recent evidence has suggested the critical role of gut microbiota in osteoimmunology, and modulation of gut microbiota may have positive influence on bone metabolisms. The present study aimed to evaluate the therapeutic effects of probiotics on alveolar bone loss under estrogen-deficient condition. Inflammatory alveolar bone loss induced by either chronic periodontitis or apical periodontitis was established in ovariectomized (OVX) rats, which were gavage-fed with probiotics daily until sacrifice. Gut microbiota and gut permeability, as well as alveolar bone loss and the related osteoimmune were evaluated to investigate the effects and underlying mechanisms by which probiotics counter the alveolar bone loss under estrogen-deficiency. ResultsWe found that administration of probiotics significantly prevented periodontal and apical bone resorption in OVX rats. Administration of probiotics significantly enriched butyrate-producing genera and enhanced gut butyrate production, resulting in improved intestinal barrier and decreased gut permeability in the OVX rats. Furthermore, the estrogen deprivation-induced inflammatory responses were suppressed in probiotics-treated OVX rats, as reflected by reduced serum levels of inflammatory cytokines and a balanced distribution of CD4+IL-17A+Th17 cells and CD4+CD25+Foxp3+Treg cells in the bone marrow. ConclusionOur data demonstrate that probiotics can effectively attenuate alveolar bone loss by modulating gut microbiota and further regulating osteoimmune, and thus represent a promising adjuvant in the treatment of alveolar bone loss under estrogen-deficiency.

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Single Local Injection of Epigallocatechin Gallate-Modified Gelatin Attenuates Bone Resorption and Orthodontic Tooth Movement in Mice

Polymers ◽

10.3390/polym10121384 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1384 ◽

Cited By ~ 6

Author(s):

Yuta Katsumata ◽

Hiroyuki Kanzaki ◽

Yoshitomo Honda ◽

Tomonari Tanaka ◽

Yuuki Yamaguchi ◽

...

Keyword(s):

Bone Resorption ◽

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Epigallocatechin Gallate ◽

Bone Destruction ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Liquid Form

Osteoclastic bone resorption enables orthodontic tooth movement (OTM) in orthodontic treatment. Previously, we demonstrated that local epigallocatechin gallate (EGCG) injection successfully slowed the rate of OTM; however, repeat injections were required. In the present study, we produced a liquid form of EGCG-modified gelatin (EGCG-GL) and examined the properties of EGCG-GL with respect to prolonging EGCG release, NF-E2-related factor 2 (Nrf2) activation, osteoclastogenesis inhibition, bone destruction, and OTM. We found EGCG-GL both prolonged the release of EGCG and induced the expression of antioxidant enzyme genes, such as heme oxygenase 1 (Hmox1) and glutamate-cysteine ligase (Gclc), in the mouse macrophage cell line, RAW264.7. EGCG-GL attenuated intracellular reactive oxygen species (ROS) levels were induced by the receptor activator of nuclear factor-kB ligand (RANKL) and inhibited RANKL-mediated osteoclastogenesis in vitro. An animal model of bone destruction, induced by repeat Lipopolysaccharide (LPS)-injections into the calvaria of male BALB/c mice, revealed that a single injection of EGCG-GL on day-1 could successfully inhibit LPS-mediated bone destruction. Additionally, experimental OTM of maxillary first molars in male mice was attenuated by a single EGCG-GL injection on day-1. In conclusion, EGCG-GL prolongs the release of EGCG and inhibits osteoclastogenesis via the attenuation of intracellular ROS signaling through the increased expression of antioxidant enzymes. These results indicate EGCG-GL would be a beneficial therapeutic approach both in destructive bone disease and in controlling alveolar bone metabolism.

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Scanning Electron Microscopy and X-Ray Analyses of Dental Tissues from a Hibernator

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100090877 ◽

1976 ◽

Vol 34 ◽

pp. 178-179

Author(s):

M. L. Zimny ◽

A. C. Haller

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Body Temperature ◽

Ground Squirrel ◽

Alveolar Bone ◽

X Ray ◽

Dental Tissues ◽

Bone Minerals ◽

Apical Tooth ◽

Scanning Electron

During hibernation the ground squirrel is immobile, body temperature reduced and metabolism depressed. Hibernation has been shown to affect dental tissues varying degrees, although not much work has been done in this area. In limited studies, it has been shown that hibernation results in (1) mobilization of bone minerals; (2) deficient dentinogenesis and degeneration of alveolar bone; (3) presence of calculus and tears in the cementum; and (4) aggrevation of caries and pulpal and apical tooth abscesses. The purpose of this investigation was to study the effects of hibernation on dental tissues employing scanning electron microscopy (SEM) and related x-ray analyses.

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