Mitochondrial Dysfunction in Periodontitis and Associated Systemic Diseases: Implications for Pathomechanisms and Therapeutic Strategies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1024 - 1024

Published: Jan. 13, 2024

Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, ligament, cementum, and alveolar bone. It arises from complex interplay between pathogenic oral bacteria host immune response. Contrary to previous view of “energy factories”, mitochondria have recently been recognized as semi-autonomous organelles that fine-tune cell survival, death, metabolism, other functions. Under physiological conditions, tissue cells participate in dynamic processes, differentiation, mineralization, regeneration. These fundamental activities depend on properly functioning mitochondria, which play crucial role through bioenergetics, dynamics, mitophagy, quality control. However, during initiation progression periodontitis, mitochondrial control compromised due range challenges, such bacterial–host interactions, inflammation, oxidative stress. Currently, mounting evidence suggests dysfunction serves common pathological mechanism linking periodontitis with systemic conditions like type II diabetes, obesity, cardiovascular diseases. Therefore, targeting intervene multiple associated diseases holds great therapeutic potential. This review provides advanced insights into Moreover, we emphasize significance diverse modulators signaling pathways regulate function cells.

Language: Английский

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The role of Mitofusin-1 and Mitofusin-2 in periodontal disease: a comprehensive review

Frontiers in Oral Health, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 17, 2025

Periodontal disease is a widespread chronic inflammatory state influencing the supporting anatomy of teeth, distinguished by oxidative stress, progressive bone loss, and tissue damage. Recent articles have highlighted significance mitochondrial dynamics, mainly Mitofusin-1 (MFN1) along with Mitofusin-2 (MFN2), inflammation regulation, homeostasis, in cellular function. The aim current study to comprehensively review including evaluate roles MFN2 MFN1 pathogenesis as well progression periodontal disease, foregrounding their effect on integrity, pathways, stress. Studies were selected depending inclusion criteria based health. Data from chosen vivo, clinical studies, vitro synthesized. Outcomes indicate that are important for preserving function, mitigating damage, fusion. Decreased levels these proteins related elevated inflammation, increased dysfunction tissues. comprehensive shows cell survival, dynamics within disease. prospective targeting therapeutic policy promising, presenting avenues upgraded management regeneration.

Language: Английский

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Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2763 - 2763

Published: Feb. 27, 2024

The extracellular matrix (ECM) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which cells sit, composed of proteins (such as collagen), glycosaminoglycans, proteoglycans, minerals, water. ECM provides fundamental framework for cellular constituents tissue biochemical support to surrounding cells. highly dynamic structure that constantly being remodeled. Matrix metalloproteinases (MMPs) are among most important proteolytic enzymes capable degrading molecules. MMPs play relevant role in physiological well pathological processes; participate embryogenesis, morphogenesis, wound healing, remodeling, therefore, their impaired activity may result several problems. MMP also associated with chronic inflammation, breakdown, fibrosis, cancer invasion metastasis. periodontium unique anatomical site, variety connective tissues, created by ECM. During periodontitis, inflammation affecting periodontium, increased presence observed, resulting irreversible losses periodontal tissues. expression be controlled various ways, one inhibition an endogenous group inhibitors (TIMPs), reversion-inducing cysteine-rich protein Kazal motifs (RECK).

Language: Английский

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An ATP-responsive metal–organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis

National Science Review, Journal Year: 2024, Volume and Issue: 11(8)

Published: June 26, 2024

ABSTRACT Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal–organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate responses and prevent tissue destruction. Addressing the challenges of synergistic effects targeted delivery faced by traditional immunomodulatory nanomaterials, Mg/Zn-MOF system is activated extracellular ATP—a pivotal molecule in pathology—ensuring release. Magnesium zinc ions released from synergistically inhibit membrane pore formation attenuating Gasdermin D (GSDMD) expression activation. action curtails pyroptosis, lactate dehydrogenase IL-1β release, thwarting onset inflammatory cascades. Mechanistically, intervenes both NLRP3/Caspase-1/GSDMD Caspase-11/GSDMD pathways mitigate pyroptosis. In vivo assessments confirm its effectiveness diminishing cell infiltration preserving collagen integrity, thereby safeguarding against periodontal damage bone loss. investigation highlights promise ion-interference strategies immunotherapy, representing a significant stride developing therapeutic approaches.

Language: Английский

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Mitochondria: An Emerging Unavoidable Link in the Pathogenesis of Periodontitis Caused by Porphyromonas gingivalis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 737 - 737

Published: Jan. 6, 2024

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Helium cold atmospheric pressure plasma reduces erastin induced inflammation and ferroptosis in human gingival fibroblasts

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 3, 2025

Oral soft tissue damage can lead to hard in the oral cavity, such as periodontal lesions, periapical disorders, cysts, and tumors. Cold plasma is known alleviate inflammation oxidative stress promote regeneration, yet effects of helium on human gingival cells remain poorly understood. In this study, we examined whether (He) cold atmospheric pressure (CAP) induce anti-inflammatory anti-ferroptotic tissues by ionizing He gas. Erastin treatment followed CAP exposure fibroblast-1 (HGF-1) reduced mRNA expression inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), which are linked inflammatory responses. Additionally, decreased nuclear receptor coactivator 4 (NCOA4) increased glutathione peroxidase (GPX4) expression. Furthermore, mitochondrial membrane potential was restored voltage-dependent anion channel 1 (VDAC1) expression, reactive oxygen species (ROS) levels mitochondria cytoplasm were reduced. These results suggest that may be associated with modulation ROS production reduction ferroptosis, but repair contributes these requires further investigation.

Language: Английский

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Porphyromonas gingivalis induces an inflammatory response via the cGAS-STING signaling pathway in a periodontitis mouse model

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 19, 2023

Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding role of Porphyromonas gingivalis ( P. ), a keystone pathogen associated with chronic periodontitis, response crucial. Herein, we investigated whether infection triggers expression type I IFN gene and various cytokines leads to activation cGAMP synthase–stimulator genes (cGAS-STING) pathway both vitro mouse model. Additionally, experimental model periodontitis using , Sting Gt mice showed lower levels bone resorption than wild-type mice. Furthermore, report that STING inhibitor (SN-011) significantly decreased cytokine production osteoclast formation . In addition, agonist (SR-717) -treated displayed enhanced macrophage infiltration M1 polarization periodontal lesions compared vehicle-treated conclusion, our results demonstrate cGAS-STING signaling may be one key mechanisms crucial for -induced periodontitis.

Language: Английский

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Insights into the Cytotoxicity and Irritant Potential of Chlorhexidine Digluconate: An In Vitro and In Ovo Safety Screening

Dentistry Journal, Journal Year: 2024, Volume and Issue: 12(7), P. 221 - 221

Published: July 17, 2024

Chlorhexidine (CHX) represents one of the most commonly used antiseptics in dentistry and other medical–pharmaceutical fields due to its broad-spectrum antimicrobial activity. However, potential toxic events arising from common use practice has become a subject increasing concern. Thus, present study was designed investigate toxicity CHX digluconate at concentrations covering antibacterial properties (0.0002–0.2%) HGF primary gingival fibroblasts, HaCaT immortalized human keratinocytes, JB6 Cl 41-5a epidermal cells, as well irritant action ovo. Our results indicate that exerted concentration- time-dependent cytotoxicity all cell lines, which evidenced by reduction viability, number, confluence, damaged membrane integrity, impaired morphology, specific apoptotic nuclear shape. The highest caused 0.02% 0.2%, concentrations, an effect on chorioallantoic also observed. novel findings revealed this research contribute overall safety profile stand basis for further investigations regard.

Language: Английский

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Active targeting microemulsion-based thermosensitive hydrogel against periodontitis by reconstructing Th17/Treg homeostasis via regulating ROS-macrophages polarization cascade

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 659, P. 124263 - 124263

Published: May 28, 2024

Language: Английский

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The Impact of Ozone on Periodontal Cell Line Viability and Function

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 72 - 72

Published: Jan. 23, 2025

Periodontal diseases, including gingivitis and periodontitis, are chronic inflammatory conditions of the teeth’ supporting structures that can lead to progressive tissue destruction loss if left untreated. Basic treatments like scaling root planing, alone or combined with antimicrobial agents, standard care. However, increasing prevalence antibiotic resistance need for new ideas in therapy, adjunctive ozone therapy have gained attention. Ozone (O3), a triatomic oxygen molecule, is used because its strong antimicrobial, anti-inflammatory, regenerative activity and, hence, as potential tool periodontal therapy. This review use disease breaks down multifaceted mechanism which includes selective action against biofilm-associated pathogens, immunomodulatory effects on host cells, stimulation repair. O3 disrupts microbial biofilms, enhances immune cell function, promotes healing by activating Nuclear Factor Erythroid 2-Related 2 (Nrf2) Mitogen-Activated Protein Kinase (MAPK) signaling pathways regulate oxidative stress, inflammation, apoptosis. Additional findings include ability upregulate growth factors extracellular matrix proteins, significant regeneration. also discusses application lines, emphasizing impact viability, proliferation, differentiation. Advances techniques, properties O3, demonstrated clinical benefits. Challenges, standardized dosages, effective delivery systems, long-term studies, addressed ensure safe integration. dual capabilities, offers an innovative approach treatment. Future research focusing optimized protocols evidence-based guidelines essential fully realize enhancing health improving patient outcomes.

Language: Английский

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