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Journal of Periodontal Research Aug 2023Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive...
BACKGROUND AND OBJECTIVE
Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive property of PDL can be attributed to its unique transcriptional profiles of cellular heterogeneity is unclear. This study aims to decipher cellular heterogeneity and distinct mechanoresponsive characteristics of odontogenic soft tissues and their underlying molecular mechanisms.
MATERIALS AND METHODS
A single-cell comparison of digested human periodontal ligament (PDL) and dental pulp (DP) was performed using scRNA-seq. An in vitro loading model was constructed to measure mechanoresponsive ability. Dual-luciferase assay, overexpression, and shRNA knockdown were used to investigate the molecular mechanism.
RESULTS
Our results demonstrate striking fibroblast heterogeneity across and within human PDL and DP. We demonstrated that a tissue-specific subset of fibroblasts existed in PDL exhibiting high expression of mechanoresponsive extracellular matrix (ECM) genes, which was verified by an in vitro loading model. ScRNA-seq analysis indicated a particularly enriched regulator in PDL-specific fibroblast subtype, Jun Dimerization Protein 2 (JDP2). Overexpression and knockdown of JDP2 extensively regulated the downstream mechanoresponsive ECM genes in human PDL cells. The force loading model demonstrated that JDP2 responded to tension and that knockdown of JDP2 effectively inhibited the mechanical force-induced ECM remodeling.
CONCLUSIONS
Our study constructed the PDL and DP ScRNA-seq atlas to demonstrate PDL and DP fibroblast cellular heterogeneity and identify a PDL-specific mechanoresponsive fibroblast subtype and its underlying mechanism.
Topics: Humans; Cells, Cultured; Single-Cell Gene Expression Analysis; Fibroblasts; Extracellular Matrix; Periodontal Ligament
PubMed: 37221903
DOI: 10.1111/jre.13139 -
Australian Dental Journal Dec 2023Patients with periodontitis often require an inter-disciplinary approach, including orthodontic treatment, for effective rehabilitation of masticatory function,... (Review)
Review
Patients with periodontitis often require an inter-disciplinary approach, including orthodontic treatment, for effective rehabilitation of masticatory function, aesthetics and quality of life. The aim of this narrative review was to comprehensively discuss literature focusing on the biology, indications and inter-disciplinary connections related to the orthodontic approach in patients with periodontitis and to present clinical concepts in accordance with valid guidelines. The outcomes of the experimental studies indicate that orthodontic tooth movement (OTM) can be performed safely for teeth with reduced periodontium, provided infection and inflammation are controlled. Orthodontic treatment can correct pathological tooth migration, is not associated with deterioration of clinical periodontal parameters and improves aesthetics. Intrusion is safe when performed with light forces and under a strict oral hygiene regimen. Teeth can be moved either towards or away from the intrabony defect previously subjected to regenerative procedures, and research suggests that OTM has the potential to enhance bone formation after regenerative therapy. The data on orthodontic movement of teeth with furcation involvement are very scarce. The improvement in furcation involvement following either combined periodontal and orthodontic treatment was only documented in animal model studies. Due to bone and tooth loss, special consideration should be given to orthodontic treatment mechanics. © 2023 Australian Dental Association.
Topics: Animals; Humans; Quality of Life; Australia; Periodontitis; Periodontium; Osteogenesis; Tooth Movement Techniques
PubMed: 37688346
DOI: 10.1111/adj.12974 -
Cellular & Molecular Biology Letters Jul 2023The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can...
BACKGROUND
The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can play a decisive role in regulating critical metabolic enzymes and pathways of stem cells. Periodontal ligament stem cells (PDLSCs) are momentous effector cells that transform mechanical force into biological signals during the reconstruction of alveolar bone. However, mechanical stimuli-induced alteration of oxidative characteristics in PDLSCs and the underlying mechanisms have not been fully elucidated.
METHODS
Herein, we examined the expression of LDH and COX4 by qRT-PCR, western blot, immunohistochemistry and immunofluorescence. We detected metabolites of lactic acid and reactive oxygen species for functional tests. We used tetramethylrhodamine methyl ester (TMRM) staining and a transmission electron microscope to clarify the mitochondrial status. After using western blot and immunofluorescence to clarify the change of DRP1, we further examined MFF, PINK1, and PARKIN by western blot. We used cyclosporin A (CsA) to confirm the regulation of mitophagy and ceased the stretching as a rescue experiment.
RESULTS
Herein, we ascertained that mechanical force could increase the level of LDH and decrease the expression of COX4 in PDLSCs. Simultaneously, the yield of reactive oxygen species (ROS) in PDLSC reduced after stretching, while lactate acid augmented significantly. Furthermore, mitochondrial function in PDLSCs was negatively affected by impaired mitochondrial membrane potential (MMP) under mechanical force, and the augment of mitochondrial fission further induced PRKN-dependent mitophagy, which was confirmed by the rescue experiments via blocking mitophagy. As a reversible physiological stimulation, the anaerobic preference of PDLSCs altered by mechanical force could restore after the cessation of force stimulation.
CONCLUSIONS
Altogether, our study demonstrates that PDLSCs under mechanical force preferred anaerobic oxidation induced by the affected mitochondrial dynamics, especially mitophagy. Our findings support an association between mechanical stimulation and the oxidative profile of stem cells, which may shed light on the mechanical guidance of stem cell maintenance and commitment, and lay a molecular foundation for periodontal tissue regeneration.
Topics: Periodontal Ligament; Anaerobiosis; Mitophagy; Reactive Oxygen Species; Oxidation-Reduction
PubMed: 37480044
DOI: 10.1186/s11658-023-00453-w -
Clinical Oral Investigations Aug 2023The aim of the present randomized controlled trial (RCT) was to evaluate the efficacy of different alveolar ridge preservation (ARP) techniques on dimensional... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The aim of the present randomized controlled trial (RCT) was to evaluate the efficacy of different alveolar ridge preservation (ARP) techniques on dimensional alterations after tooth extraction, based on clinical measurements.
BACKGROUND
Alveolar ridge preservation (ARP) is a common procedure in every day clinical practice, when dental implants are involved in treatment planning. In ARP procedures, a bone grafting material is combined with a socket sealing (SS) material in order to compensate the alveolar ridge dimensional alterations after tooth extraction. Xenograft and allograft are the most frequently used bone grafts in ARP, while free gingival graft (FGG), collagen membrane, and collagen sponge (CS) usually applied as SS materials. The evidence comparing xenograft and allograft directly in ARP procedure is scarce. In addition, FGG is usually combined with xenograft as SS material, while the evidence combing allograft with FGG is absent. Moreover, CS could probably be an alternative choice in ARP as SS material, since it has been used in previous studies but more clinical trials are required to evaluate its effectiveness.
MATERIALS AND METHODS
Forty-one patients were randomly assigned in four treatment groups: (A) freeze-dried bone allograft (FDBA) covered with collagen sponge (CS), (B) FDBA covered with free gingival graft (FGG), (C) demineralized bovine bone mineral xenograft (DBBM) covered with FGG, and (D) FGG alone. Clinical measurements were performed immediately after tooth extraction and 4 months later. The related outcomes pertained to both vertical and horizontal assessment of bone loss.
RESULTS
Overall, groups A, B, and C presented significantly less vertical and horizontal bone resorption compared to group D. No statistically significant difference was observed between allograft and xenograft, except for the vertical bone resorption at the buccal central site, where xenograft showed marginally statistically significantly reduced bone loss compared to allograft (group C vs group B: adjusted β coef: 1.07 mm; 95%CI: 0.01, 2.10; p = 0.05). No significant differences were observed in hard tissue dimensions when CS and FGG were applied over FDBA.
CONCLUSIONS
No differences between FDBA and DBBM could practically be confirmed. In addition, CS and FGG were equally effective socket sealing materials when combined with FDBA, regarding bone resorption. More RCTs are needed to compare the histological differences between FDBA and DBBM and the effect of CS and FGG on soft tissue dimensional changes.
CLINICAL RELEVANCE
Xenograft and allograft were equally efficient in ARP 4 months after tooth extraction in horizontal level. Xenograft maintained the mid-buccal site of the socket marginally better than the allograft, in vertical level. FGG and CS were equally efficient as SS materials regarding the hard tissue dimensional alterations.
TRIAL REGISTRATION
Clinical trial registration Number: NCT04934813 (clinicaltrials.gov).
Topics: Humans; Animals; Cattle; Tooth Socket; Alveolar Process; Alveolar Bone Loss; Collagen; Tooth Extraction; Alveolar Ridge Augmentation
PubMed: 37227497
DOI: 10.1007/s00784-023-05068-1 -
Clinical Oral Investigations Jan 2024To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy. (Review)
Review
OBJECTIVES
To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy.
METHODS
An electronic search (Medline, Embase and the Cochrane Library Database and OpenGray) and a hand search were carried out to identify all types of studies investigating interdental papilla reconstruction (except for reviews) with a minimum of 3 months follow-up.
RESULTS
Forty-five studies were included in the study including 7 RCTs, 2 cohort studies, 19 case series and 17 case reports. Fifteen studies reported on the use of hyaluronic acid, 6 studies on platelet-rich fibrin, 16 studies on soft tissue grafting, 4 studies on orthodontics and 4 on additional modalities. The most common outcome measures were black triangle dimensions and papillary fill percentage. Meta-analysis was not possible due to the high heterogeneity of the studies.
CONCLUSION
There are various options for interdental papilla reconstruction of which hyaluronic acid injections, PRF, surgical grafting and orthodontics seem to improve outcomes at a minimum 3 months. The use of soft tissue grafting with sub-epithelial connective tissue graft seems to be associated with the most robust evidence for the longer-term reduction of 'black triangles'. There is insufficient evidence to make recommendations to clinicians. Further research is needed in the form of well conducted RCTs with longer follow ups and patient reported outcome measures.
CLINICAL RELEVANCE
Patients frequently complain about the appearance of black triangles and their management options seem unclear. This systematic review provides insight into the available reconstructive options.
Topics: Humans; Gingiva; Hyaluronic Acid; Dental Care; Electronics
PubMed: 38231354
DOI: 10.1007/s00784-023-05409-0 -
Journal of Dentistry Nov 2023Excessive gingival display (EGD), also known as gummy smile, has various causes, including altered passive eruption (APE) and hypermobile upper lip (HUL). This... (Review)
Review
OBJECTIVES
Excessive gingival display (EGD), also known as gummy smile, has various causes, including altered passive eruption (APE) and hypermobile upper lip (HUL). This state-of-the art narrative review explores current concepts regarding soft tissue EGD etiologies and the contemporary modalities available for APE or HUL treatment.
DATA, SOURCES, STUDY SELECTION
Literature search was conducted for a narrative review on the etiology, diagnosis, and treatment of EGD caused by APE and HUL. Searching for articles was carried out in PubMed and Google Scholar. Published articles, including case reports, case series, observational and interventional clinical trials, and critical appraisals of the literature (e.g., systematic reviews) on the etiology, diagnosis, and treatment of EGD caused by APE and HUL were retrieved and reviewed. Particular focus was placed on novel treatment modalities introduced in the last five years.
CONCLUSIONS
Recent research evidence indicates that APE and HUL are the two major soft tissue-based EGD etiologies. Aesthetic crown lengthening (ACL) and lip repositioning surgery (LRS) are the established surgical treatment modalities for APE and HUL, respectively. The last few years have seen the introduction of new techniques for APE and HUL management, an expansion of the available ACL and LRS technique variations, and additional evidence further supporting the effectiveness of these two procedures. Several of the recently introduced approaches offer unique, innovative, and potentially impactful concepts. However, for many of these newly described treatments the available evidence is limited to case reports and the exact indications remain to be adequately defined.
CLINICAL SIGNIFICANCE
Altered passive eruption and hypermobile upper lip are the common soft tissue causes of gummy smile and can be successfully managed through aesthetic crown lengthening and lip repositioning surgery, respectively. A wide range of newly introduced approaches promises to further facilitate gummy smile treatment and improve outcomes.
Topics: Animals; Gingiva; Lip; Esthetics, Dental; Smiling; Hominidae
PubMed: 37730094
DOI: 10.1016/j.jdent.2023.104711 -
International Journal of Oral Science Jan 2024Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses....
Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1 mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Topics: Animals; Humans; Mice; Rats; Bone Remodeling; Caspase 1; Periodontal Ligament; Pyroptosis; Tooth Movement Techniques
PubMed: 38221531
DOI: 10.1038/s41368-023-00268-7 -
Nature Communications Jan 2024Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure,...
Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/β-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/β-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.
Topics: Animals; Mice; beta Catenin; Silicon; Porosity; Lithium; Silicic Acid; Nanowires; Dental Cementum
PubMed: 38216556
DOI: 10.1038/s41467-023-44581-5 -
ACS Applied Materials & Interfaces Sep 2023Periodontal disease is a multifactorial, bacterially induced inflammatory condition characterized by the progressive destruction of periodontal tissues. The successful...
Periodontal disease is a multifactorial, bacterially induced inflammatory condition characterized by the progressive destruction of periodontal tissues. The successful nonsurgical treatment of periodontitis requires multifunctional technologies offering antibacterial therapies and promotion of bone regeneration simultaneously. For the first time, in this study, an injectable piezoelectric hydrogel (PiezoGEL) was developed after combining gelatin methacryloyl (GelMA) with biocompatible piezoelectric fillers of barium titanate (BTO) that produce electrical charges when stimulated by biomechanical vibrations (e.g., mastication, movements). We harnessed the benefits of hydrogels (injectable, light curable, conforms to pocket spaces, biocompatible) with the bioactive effects of piezoelectric charges. A thorough biomaterial characterization confirmed piezoelectric fillers' successful integration with the hydrogel, photopolymerizability, injectability for clinical use, and electrical charge generation to enable bioactive effects (antibacterial and bone tissue regeneration). PiezoGEL showed significant reductions in pathogenic biofilm biomass (∼41%), metabolic activity (∼75%), and the number of viable cells (∼2-3 log) compared to hydrogels without BTO fillers in vitro. Molecular analysis related the antibacterial effects to be associated with reduced cell adhesion (downregulation of and ) and increased oxidative stress (upregulation of ) genes. Moreover, PiezoGEL significantly enhanced bone marrow stem cell (BMSC) viability and osteogenic differentiation by upregulating , and . In vivo, PiezoGEL effectively reduced periodontal inflammation and increased bone tissue regeneration compared to control groups in a mice model. Findings from this study suggest PiezoGEL to be a promising and novel therapeutic candidate for the treatment of periodontal disease nonsurgically.
Topics: Animals; Mice; Hydrogels; Osteogenesis; Periodontal Diseases; Periodontium; Anti-Bacterial Agents
PubMed: 37672788
DOI: 10.1021/acsami.3c08336 -
Oral Diseases Apr 2024Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor... (Review)
Review
Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor populations of alveolar bone formation will provide valuable insights into regenerative approaches to clinical practice, such as endogenous regeneration and stem-cell-based tissue engineering therapies. Classically, MSCs residing in the bone marrow, periosteum, periodontal ligament (PDL), and even the gingiva are considered to be osteogenic progenitors. Furthermore, the contributions of MSCs expressing specific markers, including Gli1, Axin2, PTHrP, LepR, and α-SMA, to alveolar bone formation have been studied using cell lineage tracing and gene knockout models. In this review, we describe the MSCs/progenitors of alveolar bone and the biological properties of different subpopulations of MSCs involved in alveolar bone development, remodeling, injury repair, and regeneration.
Topics: Humans; Mesenchymal Stem Cells; Periodontium; Osteogenesis; Periodontitis; Periodontal Ligament; Animals
PubMed: 36648363
DOI: 10.1111/odi.14507