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International Journal of Oral Science Dec 2021Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield...
Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium.
Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Topics: Colitis; Exosomes; Humans; Periodontitis; Periodontium; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 34907166
DOI: 10.1038/s41368-021-00150-4 -
Frontiers in Immunology 2022During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is...
During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is still unknown. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages during alveolar bone remodeling. We identified macrophage subclusters with specific gene expression profiles and functions. CellChat and trajectory analysis revealed a central role of the cluster during development, with the CCL signaling pathway playing a crucial role. We further demonstrated that the cluster modulated bone remodeling associated inflammation through an NF-κB dependent pathway. Blocking CCR2 could significantly reduce the Orthodontic tooth movement (OTM) progression. In addition, we confirmed the variation of CCR2 macrophages in human periodontal tissues. Our findings reveal that mechanical force-induced functional shift of the macrophages cluster mediated by NF-κB pathway, leading to a pro-inflammatory response and bone remodeling. This macrophage cluster may represent a potential target for the manipulation of OTM.
Topics: Animals; Bone Remodeling; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Periodontium; Receptors, CCR2; Sequence Analysis, RNA; Signal Transduction; Single-Cell Analysis; Tooth Movement Techniques
PubMed: 35185928
DOI: 10.3389/fimmu.2022.835986 -
Advanced Science (Weinheim,... Oct 2023Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In...
Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as a distinct periodontal ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs are located in the peri-vascular niche, possessing multilineage potential and contributing to tissue repair in response to injury. Ablation of Lepr+ PDLSCs disrupts periodontal homeostasis. Hyper-loading and unloading of occlusal forces modulate Lepr+ PDLSCs activation. Piezo1 is demonstrated that mediates the mechanosensing of Lepr+ PDLSCs by conditional Piezo1-deficient mice. Meanwhile, Yoda1, a selective activator of Piezo1, significantly accelerates periodontal tissue growth via the induction of Lepr+ cells. In summary, Lepr marks a unique multipotent PDLSC population in vivo, to contribute toward periodontal homeostasis via Piezo1-mediated mechanosensing.
Topics: Animals; Mice; Receptors, Leptin; Cell Differentiation; Periodontal Ligament; Tooth; Stem Cells; Ion Channels
PubMed: 37553778
DOI: 10.1002/advs.202303291 -
BMC Oral Health Dec 2022The effects of upper-molar distalization using clear aligners in combination with Class II elastics for anchorage reinforcement have not been fully investigated yet. The...
INTRODUCTION
The effects of upper-molar distalization using clear aligners in combination with Class II elastics for anchorage reinforcement have not been fully investigated yet. The objective of this study is to analyze the movement and stress of the whole dentition and further explore guidelines for the selection of traction methods.
METHODS
Three-dimensional (3D) finite element models are established to simulate the sequential molar distalization process, including the initial distalization of the 2 molar (Set I) and the initial distalization of the 1 molar (Set II). Each group set features three models: a control model without Class II elastics (model A), Class II elastics attached to the tooth by buttons (model B), and Class II elastics attached to the aligner by precision cutting (model C). The 3D displacements, proclination angles, periodontal ligament (PDL) hydrostatic stress and alveolar bone von Mises stress in the anterior area are recorded.
RESULTS
In all of the models, the maxillary anterior teeth are labial and mesial proclined, whereas the distal moving molars exhibit distal buccal inclination with an extrusion tendency. With the combination of Class II elastics, the anchorage was effectively reinforced; model C demonstrates superior anchorage reinforcement with lower stress distribution in comparison with model B. The upper canines in model B present an extrusion tendency. Meanwhile, the mandibular dentition in models B and C experience undesired movement tendencies with little discrepancy from each other.
CONCLUSIONS
Class II elastics are generally effective for anchorage reinforcement as the upper-molar distalization is performed with clear aligners. Class II elastics attached to an aligner by precision cutting is a superior alternative for maxillary anchorage control in cases that the proclination of upper incisors and extrusion of upper canines are unwanted.
Topics: Finite Element Analysis; Molar; Incisor; Periodontal Ligament; Orthodontic Appliances, Removable
PubMed: 36456944
DOI: 10.1186/s12903-022-02526-2 -
Genesis (New York, N.Y. : 2000) Sep 2022The periodontium is a suitable target for regenerative intervention, since it does not functionally restore itself after disease. Importantly, the limited regeneration... (Review)
Review
The periodontium is a suitable target for regenerative intervention, since it does not functionally restore itself after disease. Importantly, the limited regeneration capacity of the periodontium could be improved with the development of novel biomaterials and therapeutic strategies. Of note, the regenerative potential of the periodontium depends not only on its tissue-specific architecture and function, but also on its ability to reconstruct distinct tissues and tissue interfaces, suggesting that the advancement of tissue engineering approaches can ultimately offer new perspectives to promote the organized reconstruction of soft and hard periodontal tissues. Here, we discuss material-based, biologically active cues, and the application of innovative biofabrication technologies to regenerate the multiple tissues that comprise the periodontium.
Topics: Biocompatible Materials; Periodontal Ligament; Periodontium; Tissue Engineering
PubMed: 36113074
DOI: 10.1002/dvg.23501 -
Periodontology 2000 Feb 2024Periodontitis is a complex inflammatory disorder of the tooth supporting structures, associated with microbial dysbiosis, and linked to a number if systemic conditions.... (Review)
Review
Periodontitis is a complex inflammatory disorder of the tooth supporting structures, associated with microbial dysbiosis, and linked to a number if systemic conditions. Untreated it can result in an irreversible damage to the periodontal structures and eventually teeth loss. Regeneration of the lost periodontium requires an orchestration of a number of biological events on cellular and molecular level. In this context, a set of vitamins have been advocated, relying their beneficial physiological effects, to endorse the biological regenerative events of the periodontium on cellular and molecular levels. The aim of the present article is to elaborate on the question whether or not vitamins improve wound healing/regeneration, summarizing the current evidence from in vitro, animal and clinical studies, thereby shedding light on the knowledge gap in this field and highlighting future research needs. Although the present review demonstrates the current heterogeneity in the available evidence and knowledge gaps, findings suggest that vitamins, especially A, B, E, and CoQ, as well as vitamin combinations, could exert positive attributes on the periodontal outcomes in adjunct to surgical or nonsurgical periodontal therapy.
Topics: Humans; Wound Healing; Vitamins; Animals; Regeneration; Periodontitis; Periodontium
PubMed: 37592831
DOI: 10.1111/prd.12513 -
Genesis (New York, N.Y. : 2000) Sep 2022The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a... (Review)
Review
The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a prevalent infectious disease of the periodontium, threatens the integrity of these tissues and causes irreversible damage. Periodontal therapy aims to repair and ultimately regenerate these tissues toward preserving native dentition and improving the physiologic integration of dental implants. The PDL contains multipotent stem cells, which have a robust capacity to differentiate into various types of cells to form the PDL, cementum, and alveolar bone. Selection of appropriate growth factors and biomaterial matrices to facilitate periodontal regeneration are critical to recapitulate the physiologic organization and function of the periodontal complex. Herein, we discuss the current state of clinical periodontal regeneration including a review of FDA-approved growth factors. We will highlight advances in preclinical research toward identifying additional growth factors capable of robust repair and biomaterial matrices to augment regeneration similarly and synergistically, ultimately improving periodontal regeneration's predictability and long-term efficacy. This review should improve the readers' understanding of the molecular and cellular processes involving periodontal regeneration essential for designing comprehensive therapeutic approaches.
Topics: Biocompatible Materials; Dental Implants; Periodontal Ligament; Periodontium; Tissue Engineering
PubMed: 36086991
DOI: 10.1002/dvg.23499 -
Advanced Pharmaceutical Bulletin Jul 2023Periodontal disease is the most common oral disease. This disease can be considered as an inflammatory disease. The immune response to bacteria accumulated in the gum... (Review)
Review
Periodontal disease is the most common oral disease. This disease can be considered as an inflammatory disease. The immune response to bacteria accumulated in the gum line plays a key role in the pathogenesis of periodontal disease. In addition to immune cells, periodontal ligament cells and gingival epithelial cells are also involved in the pathogenesis of this disease. miRNAs which are small RNA molecules with around 22 nucleotides have a considerable relationship with the immune system affecting a wide range of immunological events. These small molecules are also in relation with periodontium tissues especially periodontal ligament cells. Extensive studies have been performed in recent years on the role of miRNAs in the pathogenesis of periodontal disease. In this review paper, we have reviewed the results of these studies and discussed the role of miRNAs in the immunopathogenesis of periodontal disease comprehensively. miRNAs play an important role in the pathogenesis of periodontal disease and maybe helpful therapeutic targets for the treatment of periodontal disease.
PubMed: 37646047
DOI: 10.34172/apb.2023.048 -
Cells Oct 2022Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many... (Review)
Review
Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many inflammatory cytokines secreted by immune or tissue cells, such as interleukin-6. In contrast, gingival overgrowth develops as a side effect of specific drugs, such as immunosuppressants, anticonvulsants, and calcium channel blockers. Human gingival fibroblasts (HGFs) are the most abundant cells in gingival connective tissue, and human periodontal ligament fibroblasts (HPLFs) are located between the teeth and alveolar bone. HGFs and HPLFs are both crucial for the remodeling and homeostasis of periodontal tissue, and their roles in the pathogenesis of periodontal diseases have been examined for 25 years. Various responses by HGFs or HPLFs contribute to the progression of periodontal diseases. This review summarizes the biological effects of HGFs and HPLFs on the pathogenesis of periodontal diseases.
Topics: Humans; Gingiva; Fibroblasts; Periodontal Ligament; Periodontitis; Gingival Overgrowth
PubMed: 36359741
DOI: 10.3390/cells11213345