Identification of a new genetic variant (G231N, E232T, N235D) of peptidylarginine deiminase from P. gingivalis in advanced periodontitis.

Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic diseases, including rheumatoid arthritis (RA). Porphyromonas gingivalis, one of the bacterial species implicated in CP as a keystone pathogen produces peptidyl arginine deiminase (PPAD) that citrullinates C-terminal arginine residues in proteins and peptides. Autoimmunity to citrullinated epitopes is crucial in RA, hence PPAD activity is considered a possible mechanistic link between CP and RA. Here we determined the PPAD enzymatic activity produced by clinical isolates of P. gingivalis, sequenced the ppad gene, and correlated the results with clinical determinants of CP in patients from whom the bacteria were isolated. The analysis revealed variations in PPAD activity and genetic diversity of the ppad gene in clinical P. gingivalis isolates. Interestingly, the severity of CP was correlated with a higher level of PPAD activity that was associated with the presence of a triple mutation (G231N, E232T, N235D) in PPAD in comparison to W83 and ATCC 33277 type strains. The relation between mutations and enhanced activity was verified by directed mutagenesis which showed that all three amino acid residue substitutions must be introduced into PPAD expressed by the type strains to obtain the super-active enzyme. Cumulatively, these results may lead to the development of novel prognostic tools to assess the progress of CP in the context of associated RA by analyzing the ppad genotype in CP patients infected with P. gingivalis.

[Periodontal tissue regeneration: current therapeutic strategies and future directions in further research].

Chronic and progressive destruction/damage of the periodontal tissues resulted from periodontitis is the leading cause of tooth loss in adults. Traditional periodontal therapies such as scaling and root planning or flap surgery have demonstrated effective in controlling local inflammation and in suppressing/arresting the disease progression of periodontitis. However, those infection control measures cannot help to regenerate lost periodontal tissues to a statistically or clinically significant degree. Although some successes regarding the reduction of the intrabony defect and maintenance of the periodontal homeostasis have been achieved in periodontal regenerative procedures, comprising but not limited to guided tissue regeneration (GTR) or bone grafting technique, the restorative effectiveness of the architecture and function of the lost or injured tissues is far from our clinical expectation. The use of the concept, technique, and method of tissue engineering for periodontal regeneration is a hotspot and animal studies have shown interesting outcomes in terms of functional regeneration of lost/damaged support tissues in the periodontium, including alveolar bone, periodontal ligament, and cementum. However, numerous issues need to be addressed before those regenerative approaches can be responsibly transformed to novel clinical therapies. Recently, paradigm that induces homing of host stem cells to site of the periodontium and encourage the body's innate capability to repair is a new research field termed endogenous regeneration. Given that endogenous regenerative technique avoids ex-vivo cell culture and transplantation, it should be relatively easier to be used in the treatment of clinical patients. Due to the limited oral microenvironment and harsh periodontal local condition for tissue regeneration, as well as poor understanding of periodontal regenerative biology, there is still a long way ahead to explore new effective, practical, and economical therapies to save and protect natural tooth and for combating highly prevalent periodontal disease.

Matrix Metalloproteinases in the Periodontium-Vital in Tissue Turnover and Unfortunate in Periodontitis.

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

Oral manifestations in women using hormonal contraceptive methods: a systematic review.

OBJECTIVES: To investigate the oral manifestations in women of reproductive age using hormonal contraceptive methods. MATERIALS AND METHODS: This review is based on the PRISMA statement. A literature search incorporated observational studies from the last 21 years. An investigative question was formulated using the PICO model, studies were selected, and a quality analysis was performed using the modified STROBE guidelines. A bibliometric analysis was performed, and the data were examined. RESULTS: Thirteen articles were included, with the majority evaluating periodontal status. Others analyzed factors such as the presence of alveolar osteitis, oral candidiasis, and salivary microbiome dysbiosis. Ten articles were deemed to have a low risk of bias. CONCLUSIONS: Hormonal contraceptives may increase the risk of alveolar osteitis following tooth extraction and increase the presence of the Candida species in the oral cavity. They also affect the periodontium, such as the frequent development of gingivitis, but do not lead to changes in the salivary microbiome. CLINICAL RELEVANCE: The increasing number of women using hormonal contraceptives and the knowledge that these contraceptives can produce oral cavity alterations underscore the need to evaluate the oral manifestations found in these women.

Circ_0036490 and DKK1 competitively bind miR-29a to promote lipopolysaccharides-induced human gingival fibroblasts injury.

MicroRNA (miRNA) plays a regulatory role in periodontitis. This study aimed to explore whether miR-29a could affect lipopolysaccharides (LPSs)-induced injury in human gingival fibroblasts (HGFs) through the competitive endogenous RNAs (ceRNA) mechanism. Periodontal ligament (PDL) tissues and HGFs were derived from patients with periodontitis and healthy volunteers. Periodontitis cell model was established by treating HGFs with LPS. Expression levels of circ_0036490, miR-29a, and DKK1 were evaluated by the reverse transcription quantitative real-time PCR (RT-qPCR) method. Western blotting assay was performed to assess protein expression levels of pyroptosis-related proteins and Wnt signalling related proteins. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Concentration of lactate dehydrogenase (LDH), interleukin (IL)-1ß, and IL-18 were determined by Enzyme-linked immunosorbent assay (ELISA). Pyroptosis rate were determined by flow cytometry assay to evaluate pyroptosis. The interaction between miR-29a and circ_0036490 or DKK1 was verified by dual-luciferase reporter and RNA pull-down assays. MiR-29a expression was lower in PDL tissues of patients with periodontitis than that in healthy group; likewise, miR-29a was also downregulated in LPS-treated HGFs. Overexpression of miR-29a increased cell viability and decreased pyroptosis of HGFs induced by LPS while inhibition of miR-29a exerted the opposite role. MiR-29a binds to circ_0036490 and elevation of circ_0036490 contributed to dysfuntion of LPS-treated HGFs and reversed the protection function of elevated miR-29a. In addition, miR-29a targets DKK1. Overexpression of DKK1 abrogated the effects of overexpressed miR-29a on cell vaibility, pyroptosis, and protein levels of Wnt signalling pathway of LPS-treated HGFs. Circ_0036490 and DKK1 competitively bind miR-29a to promote LPS-induced HGF injury in vitro. Wnt pathway inactivated by LPS was activated by miR-29a. Thence, miR-29a may be a promising target for periodontitis.

The repeatability of periodontal imaging with intraoral ultrasound scanning.

OBJECTIVE: Ultrasound is a non-invasive and low-cost diagnostic tool widely used in medicine. Recent studies have demonstrated that ultrasound imaging might have the potential to be used intraorally to assess the periodontium by comparing it to current imaging methods. This study aims to characterize the repeatability of intraoral periodontal ultrasound imaging. MATERIALS AND METHODS: Two hundred and twenty-three teeth were scanned from fourteen volunteers participating in this study. One operator conducted all the scans in each tooth thrice with a 20 MHz intraoral ultrasound. The repeatability of three measurements, alveolar bone crest to the cementoenamel junction (ABC-CEJ), gingival thickness (GT), and alveolar bone thickness (ABT), was calculated with intercorrelation coefficient (ICC). Measurements were also compared with mean absolute deviation (MAD), repeatability coefficient (RC), and descriptive statistics. RESULTS: ICC scores for intra-rater repeatability were 0.917(0.897,0.933), 0.849(0.816,0.878), and 0.790(0.746,0.898), MAD results were 0.610 mm (± 0.508), 0.224 (± 0.200), and 0.067 (± 0.060), and RC results were 0.648, 0.327, and 0.121 for ABC-CEJ, GT, and ABT measurements, respectively. CONCLUSION: Results of the present study pointed towards good or excellent repeatability of ultrasound as a measurement tool for periodontal structures. CLINICAL RELEVANCE: Clinicians could benefit from the introduction of a novel chairside diagnostic tool. Ultrasound is a non-invasive imaging assessment tool for the periodontium with promising results in the literature. Further validation, establishment of scanning protocols, and commercialization are still needed before ultrasound imaging is available for clinicians.

Influence of fixed orthodontic steel retainers on gingival health and recessions of mandibular anterior teeth in an intact periodontium - a randomized, clinical controlled trial.

OBJECTIVE: Aim of this randomized clinical controlled trial was to evaluate the influence of fixed orthodontic steel retainers on gingival health and recessions of mandibular anterior teeth. MATERIALS AND METHODS: After end of the orthodontic treatment, patients were randomly assigned into the test (fixed steel retainer) or control group (modified removable vacuum-formed retainer). Periodontal parameters (periodontal probing depth: PPD; recession: REC; bleeding on probing: BOP) as well as plaque and gingival index were assessed on mandibular anterior teeth directly before attaching/handing over the retainer (baseline: BL), 6 and 12 months after orthodontic treatment. RESULTS: 37 patients (test: n = 15, mean age: 16.1±4.2 years; control: n = 17, mean age: 17.1±5.4 years) completed the study. REC and PPD failed to show significant pairwise differences. The number of patients showing gingival health in the area of the mandibular anterior teeth (test: BL n = 10, 6 months n = 9, 12 months n = 11; control: BL n = 10, 6 months n = 16, 12 months n = 15) revealed a significant difference for the intra-group comparison between BL and 6 months in the control group (p = 0.043). The inter-group comparisons failed to show significant differences. CONCLUSION: Young orthodontically treated patients with fixed steel retainers show in 73.3% healthy gingival conditions after one year which are comparable to the control group (88.2%). Gingival recessions were in a clinically non-relevant range at any time of the examination. CLINICAL TRIAL NUMBER: DRKS00016710.

[Bioactive materials in periodontal regeneration].

Bioactive materials are a type of biomaterials that can generate special biological or chemical reactions on the surface or interface of materials. These reactions can impact the interaction between tissues and materials, stimulate cell activity, and guide tissue regeneration. In recent years, bioactive materials have been widely used in periodontal tissue regeneration. This review aims to consolidate the definition and characteristics of bioactive materials, as well as summarize their utilization in periodontal tissue regeneration. These findings shed new light on the application of bioactive materials in this field.

Periodontium-Mimicking, Multifunctional Biomass-Based Hydrogel Promotes Full-Course Socket Healing.

Preserving stable tooth-periodontal tissue integration is vital for maintaining alveolar bone stability under physiological conditions. However, tooth extraction compromises this integration and impedes socket healing. Therefore, it becomes crucial to provide early stage coverage of the socket to promote optimal healing. Drawing inspiration from the periodontium, we have developed a quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel, termed the quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel (QDL hydrogel). Through blue-light-induced cross-linking, the QDL hydrogel serves as a comprehensive wound dressing for socket healing. The QDL hydrogel exhibits remarkable efficacy in closing irregular tooth extraction wounds. Its favorable mechanical properties, flexible formability, and strong adhesion are achieved through modifications of chitosan and sodium alginate derived from biomass sources. Moreover, the QDL hydrogel demonstrates a superior hemostatic ability, facilitating swift blood clot formation. Additionally, the inherent antibacterial properties of the QDL hydrogel effectively inhibit oral microorganisms. Furthermore, the QDL hydrogel promotes angiogenesis, which facilitates the nutrient supply for subsequent tissue regeneration. Notably, the hydrogel accelerates socket healing by upregulating the expression of genes associated with wound healing. In conclusion, the periodontium-mimicking multifunctional hydrogel exhibits significant potential as a clinical tooth extraction wound dressing.

Dental and periodontal dimensions stability after esthetic clinical crown lengthening surgery: a 12-month clinical study.

OBJECTIVES: To evaluate the stability of periodontal tissues 3 (T3), 6 (T6), and 12 (T12) months after esthetic crown lengthening (ACL) and the possible correlations between changes in those structures. MATERIALS AND METHODS: Twenty individuals were evaluated through clinical assessment, photography, and tomography. Measurements included gingival margin (GM), clinical crown length (CCL), interdental papilla height (PH) and width (PW), gingival thickness (GT), bone thickness (BT), probing depth (PD), distance between alveolar crest and GM, distance between alveolar crest and cementoenamel junction. Nonparametric and correlation statistics were performed (p < 0.05). RESULTS: CCL at T0 was 7.42 ± 0.70 mm and increased to 9.48 ± 0.49 mm immediately after ACL, but it decreased to 8.93 ± 0.65 mm at T12. PD decreased 0.60 mm from T0 to T6, and it increased 0.39 mm from T6 to T12. BT decreased 0.20 mm, while GT increased 0.29 mm from T0 to T12. Both PW and PH showed enlargement in T12. A positive moderate correlation was found between CCL/T0 and CCL/T12, GT/T0 and AC-GM/T12, BT/T0 and GT/T12. A few negative moderate correlations were PD/T0 and CCL/T12, PD/T0 and PH/T0, PD/T0 and BT/T12. CONCLUSIONS: ACL procedure was effective. Although some rebound occurred, that was not clinically important. PD tended to reestablish its original length, partially due to a migration of GM during the healing period. Besides, a thickening of supracrestal soft tissues was observed. CLINICAL RELEVANCE: The present study centers on the factors influencing the stability of periodontal tissues after esthetic crown lengthening, underscoring the procedure's influence on esthetics and biology and the need for careful treatment planning.

Gli1+ Periodontal Mesenchymal Stem Cells in Periodontitis.

Periodontal mesenchymal stem cells (MSCs) play a crucial role in maintaining periodontium homeostasis and in tissue repair. However, little is known about how periodontal MSCs in vivo respond under periodontal disease conditions, posing a challenge for periodontium tissue regeneration. In this study, Gli1 was used as a periodontal MSC marker and combined with a Gli1-cre ERT2 mouse model for lineage tracing to investigate periodontal MSC fate in an induced periodontitis model. Our findings show significant changes in the number and contribution of Gli1+ MSCs within the inflamed periodontium. The number of Gli1+ MSCs that contributed to periodontal ligament homeostasis decreased in the periodontitis-induced teeth. While the proliferation of Gli1+ MSCs had no significant difference between the periodontitis and the control groups, more Gli1+ MSCs underwent apoptosis in diseased teeth. In addition, the number of Gli1+ MSCs for osteogenic differentiation decreased during the progression of periodontitis. Following tooth extraction, the contribution of Gli1+ MSCs to the tooth socket repair was significantly reduced in the periodontitis-induced teeth. Collectively, these findings indicate that the function of Gli1+ MSCs in periodontitis was compromised, including reduced contribution to periodontium homeostasis and impaired injury response.

Calcitonin gene-related peptide regulates periodontal tissue regeneration.

Calcitonin gene-related peptide (CGRP), a neuropeptide composed of 37 amino acids secreted from the sensory nerve endings, reportedly possesses various physiological effects, such as vasodilation and neurotransmission. Recently, there have been increasing reports of the involvement of CGRP in bone metabolism; however, its specific role in the pathogenesis of periodontitis, particularly in the repair and healing processes, remains to be elucidated. Therefore, this study aimed to investigate dynamic expression patterns of CGRP during the destruction and regeneration processes of periodontal tissues in a mouse model of experimental periodontitis. We also explored the effects of CGRP on periodontal ligament cells, which can differentiate to hard tissue-forming cells (cementoblasts or osteoblasts). Our findings demonstrated that CGRP stimulation promotes the differentiation of periodontal ligament cells into hard tissue-forming cells. Experimental results using a ligature-induced periodontitis mouse model also suggested fluctuations in CGRP expression during periodontal tissue healing, underscoring the vital role of CGRP signaling in alveolar bone recovery. The study results highlight the important role of nerves in the periodontal ligament not only in sensory reception in the periphery, as previously known, but also in periodontal tissue homeostasis and tissue repair processes.

[Regional immunity involved in the maintenance and imbalance of periodontal homeostasis].

The concept of homeostatic medicine has helped the researchers to understand the periodontal tissues in a completely new dimension. Periodontal tissues are subjected to complex external environmental stimuli and the internal tissues are continuously undergoing active remodeling. Periodontal regional immunity is continuously activated by local stimuli and interacts with the epithelial barrier, stromal tissue/extracellular matrix, and bone-coupled systems in a complex manner. Together, this complex network shapes the periodontal homeostasis. Under physiological conditions, moderate regional immunity relies on barrier function, intrinsic immune cells to control periodontal microbiota and maintain homeostasis. Under pathological conditions, pathogenic microbiota drive the periodontal homeostasis imbalance through over-activated regional immunity such as neutrophils, helper T (Th) 17 cells and B cells, causing periodontitis. Using the most basic immunological classification as a framework, this paper provides a systematic overview of the above mechanisms by which regional immunity regulates periodontal homeostasis, reviews the translational studies that have been carried out on homeostatic remodeling strategies targeting regional immunity, and proposes a series of periodontal homeostasis medicine research directions worth exploring, as well as potential new targets and strategies for homeostatic remodeling.

Association between periodontitis and inflammatory comorbidities: The common role of innate immune cells, underlying mechanisms and therapeutic targets.

Periodontitis, which is related to various systemic diseases, is a chronic inflammatory disease caused by periodontal dysbiosis of the microbiota. Multiple factors can influence the interaction of periodontitis and associated inflammatory disorders, among which host immunity is an important contributor to this interaction. Innate immunity can be activated aberrantly because of the systemic inflammation induced by periodontitis. This aberrant activation not only exacerbates periodontal tissue damage but also impairs systemic health, triggering or aggravating inflammatory comorbidities. Therefore, innate immunity is a potential therapeutic target for periodontitis and associated inflammatory comorbidities. This review delineates analogous aberrations of innate immune cells in periodontitis and comorbid conditions such as atherosclerosis, diabetes, obesity, and rheumatoid arthritis. The mechanisms behind these changes in innate immune cells are discussed, including trained immunity and clonal hematopoiesis of indeterminate potential (CHIP), which can mediate the abnormal activation and myeloid-biased differentiation of hematopoietic stem and progenitor cells. Besides, the expansion of myeloid-derived suppressor cells (MDSCs), which have immunosuppressive and osteolytic effects on peripheral tissues, also contributes to the interaction between periodontitis and its inflammatory comorbidities. The potential treatment targets for relieving the risk of both periodontitis and systemic conditions are also elucidated, such as the modulation of innate immunity cells and mediators, the regulation of trained immunity and CHIP, as well as the inhibition of MDSCs' expansion.

To intrude or not to intrude? A systematic review of the controversy surrounding orthodontic intrusion on reduced periodontium.

OBJECTIVE: The main objective of this review was to evaluate the effects of orthodontic intrusion on patients with reduced periodontium. Additionally, this review aims to explore the potential for attachment gain and tissue regeneration in these patients and identify optimal therapeutic conditions to mitigate any negative effects of intrusion. METHODS: A systematic review was conducted according to the PRISMA 2020 statement. Duplicate electronic searches of the PubMed, Cochrane, EMC Premium, and Science Direct databases were performed by two independent reviewers. Data extraction and quality assessments, including risk of bias evaluation using the Cochrane and ROBINS-I tools were conducted. RESULTS: From an initial pool of 418 articles, 29 were selected after title and abstract screening for full-text review. Following thorough full-text reading, 15 studies were ultimately included in the analysis. The total number of patients included in the studies is 528, who underwent orthodontic intrusion on reduced periodontium. Studies indicated a decrease in periodontal pocket depth and an increase in clinical attachment with ortho-periodontal treatment. Alveolar bone level outcomes varied, showing both increases and losses. Authors generally observed improved papillary regeneration and reduced gingival recessions. CONCLUSION: Clinical studies involving combined ortho-periodontal treatment showed that orthodontic intrusion on a reduced but healthy periodontium can be considered a beneficial treatment for the periodontium, provided that potential adverse effects are carefully monitored.

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

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

New insights into nanotherapeutics for periodontitis: a triple concerto of antimicrobial activity, immunomodulation and periodontium regeneration.

Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.

LRP1-deficient leptin receptor-positive cells in periodontal ligament tissue reduce alveolar bone mass by inhibiting bone formation.

OBJECTIVE: Leptin receptor-positive (LepR+) periodontal ligament (PDL) cells play a crucial role in osteogenesis during tooth socket healing and orthodontic tooth movement; however, the factors regulating osteoblast differentiation remain unclear. This study aimed to demonstrate the function of low-density lipoprotein receptor-related protein 1 (LRP1) in alveolar bone formation by examining conditional knockout (cKO) mice lacking LRP1 in LepR+ cells. DESIGN: Bone mass and formation were examined via bone morphometric analysis. Bone formation and resorption activities were determined via histochemical staining. Additionally, PDL cells collected from molars were induced to differentiate into osteoblasts with the addition of BMP2 and to mineralize with the addition of osteogenic medium. Osteoblast differentiation of PDL cells was examined by measuring the expression of osteoblast markers. RESULTS: Bone morphometry analysis revealed decreased mineral apposition rate and alveolar bone mass in cKO mice. Additionally, cKO mice showed a decreased number of osterix-positive cells in the PDL. cKO mice had a large number of osteoclasts around the alveolar bone near the root apex and mesial surface of the tooth. In the PDL cells from cKO mice, inhibition of mineralized matrix formation and decreased expression of alkaline phosphatase, osterix, bone sialoprotein, and osteocalcin were observed even when BMP2 was added to the medium. BMP2, BMP4, and osteoprotegerin expression also decreased, but RANKL expression increased dominantly. CONCLUSION: LRP1 in LepR+ cells promotes bone formation by stimulating osteoblast differentiation. Our findings can contribute to clinical research on bone diseases and help elucidate bone metabolism in the periodontal tissue.

Use of ultrasound imaging for assessment of the periodontium: A systematic review.

The objective of this study was to systematically review the literature regarding diagnostic applications of ultrasound imaging for evaluation of the periodontium in humans. The search was conducted on Medline, EMBASE, Web of Science, Scopus, Cochrane, and PubMed up to April 3, 2023. The studies included were exclusively human studies that assessed the periodontium with ultrasound (US) imaging (b-mode). Outcomes measured included alveolar bone level, alveolar bone thickness, gingival thickness, and blood flow quantification. References were imported to Covidence. Two reviewers conducted phases 1 and 2. The JBI risk assessment tool for cross-sectional studies was used. Extracted data included the transducer and measurements used and the study's outcomes. The search yielded 4892 studies after removing duplicates. From these, 25 studies were included and selected for extraction. Included studies retrieved outcomes from US examinations of the periodontal tissues. From the selected studies, 15 used US on natural teeth, 4 used US on implants, 2 used US on edentulous ridges, and 4 used color flow/power in US to evaluate the blood flow. The results of the present systematic review suggest that US might be a feasible and valuable diagnostic tool for the periodontium, with the potential to complement shortfalls of current radiographic technologies.

Hierarchically patterned triple-layered gelatin-based electrospun membrane functionalized by cell-specific extracellular matrix for periodontal regeneration.

OBJECTIVES: Regenerating the periodontium poses a critical challenge in oral medicine. To repair various periodontal defects, it is necessary to adopt a bio-scaffold that provides both the architecture and bioactive cues for local stem cells to migrate, reside, proliferate, and differentiate. The objective of this study is to combine a cell-specific decellularized extracellular matrix (ECM) and a biomimetic electrospinning scaffold to regenerate severely destructed periodontium. METHODS: SEM, water contact angle (WCA), live/dead staining, swelling ratio, tensile test and immune-fluorescent staining were used to define the suitable topography for certain dental stem cells seeding and culturing. Transwell assay, CCK-8, Alizarin Red staining and PCR immune-fluorescent staining were used to determine ideal cell-specific ECM for PDLSCs/BMSCs migration, viability, and oriented differentiation. A biodegradable triple-layered electrospun scaffold (TLS) was fabricated by electrospinning with aligned fibers on both surfaces and a polyporous structure in the middle. The morphology and inter-porous structure of the TLS were characterized by SEM and mercury intrusion porosimetry (MIP). The surface of the TLS was functionalized with cell-specific ECM (Bi-ECM-TLS) through decellularization of the cell sheets cultured on the scaffold. The regenerative outcome of Bi-ECM-TLS was assessed by an in-situ rat periodontal defect model. Micro-CT, HE-staining, Masson's trichome staining, Sirius Red staining and Immunofluorescent staining were used for histological analysis. RESULTS: Aligned Gelatin/PCL fibrous membrane (GPA) was most effective for both PDLSCs and BMSCs in culture with WCA around 50 degrees and better mechanical strength than the rest. MSCs favored the same type of ECM (cell-specific ECM), and their regenerative properties were effectively induced with better chemotaxis, proliferative and differentiating behaviors. TLS characterization showed that TLS possessed aligned-random-aligned structure and inter-porous structure. In a rat model of periodontal defects, the TLS functionalized by BMSC-specific ECM for bone regeneration and PDLSC-specific ECM demonstrated highest BV/TV ratio, best bone structure and ligament fiber orientation and blood vessel formation, suggesting optimal performance in regenerating both alveolar bone and periodontal ligaments over TLS, single-ECM loaded TLS and r-Bi-ECM-TLS. SIGNIFICANCE: This study highlights the importance of combining a cell-specific decellularized ECM and a biomimetic electrospinning scaffold for targeted periodontal tissue regeneration, with potential implications for periodontal tissue engineering and improved patient outcomes.