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Advanced Science (Weinheim,... Sep 2023Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a...
Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a crucial role in inflammatory response. An appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) macrophages is indispensable for treating periodontitis. As M2 macrophage-derived exosomes (M2-exos) can actively target inflammatory sites and modulate immune microenvironments, M2-exos can effectively treat periodontitis. Excessive endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) are highly destructive pathological characteristics during inflammatory periodontal bone loss. Although melatonin has antioxidant and anti-inflammatory effects, studies focusing on melatonin ER stress modulation remain limited. This study fabricates engineered M2-exos loading with melatonin (Mel@M2-exos) for treating periodontitis. As a result, M2-exos drive an appropriate and timely macrophage reprogramming from M1 to M2 type, which resolves chronic inflammation and accelerated periodontal healing. Melatonin released from Mel@M2-exos rescues the osteogenic and cementogenic differentiation capacity in inflammatory human periodontal ligament cells (hPDLCs) by reducing excessive ER stress and UPR. Injectable gelatin methacryloyl (GelMA) hydrogels with sustained-release Mel@M2-exos accelerate periodontal bone regeneration in rats with ligation-induced periodontitis. Taken together, melatonin engineering M2 macrophage-derived exosomes are promising candidates for inflammatory periodontal tissue regeneration.
Topics: Rats; Humans; Animals; Melatonin; Exosomes; Periodontitis; Endoplasmic Reticulum Stress; Inflammation; Macrophages
PubMed: 37452425
DOI: 10.1002/advs.202302029 -
International Journal of Nanomedicine 2023Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with...
Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats.
PURPOSE
Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism.
METHODS
DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1β, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining.
RESULTS
DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis.
CONCLUSION
DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.
Topics: Animals; Rats; Periodontal Ligament; Alveolar Bone Loss; Dental Pulp; Exosomes; Interleukin-6; Osteogenesis; Periodontitis; Anti-Inflammatory Agents; Inflammation
PubMed: 37608819
DOI: 10.2147/IJN.S420967 -
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 -
Antibiotics (Basel, Switzerland) Nov 2023Cannabinoids are a well-documented treatment modality for various immune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease, Crohn's... (Review)
Review
INTRODUCTION
Cannabinoids are a well-documented treatment modality for various immune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease, Crohn's disease, arthritis, multiple sclerosis, and a range of neurodegenerative conditions. However, limited information is available regarding the therapeutic potential of cannabinoids in treating periodontal disease.
OBJECTIVE
The objective of this study is to analyze the current evidence on the antibacterial and immunomodulatory effects of cannabis and its role in the healing and regeneration processes within periodontal tissues.
RESULTS
This review discusses the potential role of cannabinoids in restoring periodontal tissue homeostasis.
CONCLUSIONS
The examination of the endocannabinoid system and the physiological effects of cannabinoids in the periodontium suggests that they possess immunomodulatory and antibacterial properties, which could potentially promote proper tissue healing and regeneration.
PubMed: 38136721
DOI: 10.3390/antibiotics12121687 -
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 -
Bioengineering (Basel, Switzerland) Nov 2023Periodontitis is a chronic inflammatory disease with a high incidence and severity in the elderly population, making it a significant public health concern. Ageing is a... (Review)
Review
Periodontitis is a chronic inflammatory disease with a high incidence and severity in the elderly population, making it a significant public health concern. Ageing is a primary risk factor for the development of periodontitis, exacerbating alveolar bone loss and leading to tooth loss in the geriatric population. Despite extensive research, the precise molecular mechanisms underlying the relationship between ageing and periodontitis remain elusive. Understanding the intricate mechanisms that connect ageing and inflammation may help reveal new therapeutic targets and provide valuable options to tackle the challenges encountered by the rapidly expanding global ageing population. In this review, we highlight the latest scientific breakthroughs in the pathways by which inflammaging mediates the decline in periodontal function and triggers the onset of periodontitis. We also provide a comprehensive overview of the latest findings and discuss potential avenues for future research in this critical area of investigation.
PubMed: 38002398
DOI: 10.3390/bioengineering10111274 -
Bioactive Materials Mar 2024Type 2 diabetes mellitus (T2DM) exacerbates irreversible bone loss in periodontitis, but the mechanism of impaired bone regeneration caused by the abnormal metabolic...
Type 2 diabetes mellitus (T2DM) exacerbates irreversible bone loss in periodontitis, but the mechanism of impaired bone regeneration caused by the abnormal metabolic process of T2DM remains unclear. Exosomes are regarded as the critical mediator in diabetic impairment of regeneration via organ or tissue communication. Here, we find that abnormally elevated exosomes derived from metabolically impaired liver in T2DM are significantly enriched in the periodontal region and induced pyroptosis of periodontal ligament cells (PDLCs). Mechanistically, fatty acid synthase (Fasn), the main differentially expressed molecule in diabetic exosomes results in ectopic fatty acid synthesis in PDLCs and activates the cleavage of gasdermin D. Depletion of liver Fasn effectively mitigates pyroptosis of PDLCs and alleviates bone loss. Our findings elucidate the mechanism of exacerbated bone loss in diabetic periodontitis and reveal the exosome-mediated organ communication in the "liver-bone" axis, which shed light on the prevention and treatment of diabetic bone disorders in the future.
PubMed: 38024229
DOI: 10.1016/j.bioactmat.2023.10.022