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The literature presents insufficient data evaluating the displacement and micromotion effects resulting from the combined use of tooth-implant connections in fixed partial dentures. Analyzing the biomechanical behavior of tooth-implant fixed partial denture (FPD) prothesis is vital for achieving an optimum design and successful clinical implementation. The objective of this study was to determine the relative significance of connector design on the displacement and micromotion of tooth-implant-supported fixed dental prostheses under occlusal vertical loading. A unilateral Kennedy class I mandibular model was created using a 3D reconstruction from CT scan data. Eight simulated designs of tooth-implant fixed partial dentures (FPDs) were split into two groups: Group A with rigid connectors and Group B with non-rigid connectors. The models were subjected to a uniform vertical load of 100 N. Displacement, strain, and stress were computed using finite element analysis. The materials were defined as isotropic, homogeneous, and exhibiting linear elastic properties. This study focused on assessing the maximum displacement in various components, including the bridge, mandible, dentin, cementum, periodontal ligament (PDL), and implant. Displacement values were predominantly higher in Group B (non-rigid) compared to Group A (rigid) in all measured components of the tooth-implant FPDs. Accordingly, a statistically significant difference was observed between the two groups at the FPD bridge (p value = 0.021 *), mandible (p value = 0.021 *), dentin (p value = 0.043 *), cementum (p value = 0.043 *), and PDL (p value = 0.043 *). Meanwhile, there was an insignificant increase in displacement values recorded in the distal implant (p value = 0.083). This study highlighted the importance of connector design in the overall stability and performance of the prosthesis. Notably, the 4.7 mm × 10 mm implant in Group B showed a displacement nearly 92 times higher than its rigid counterpart in Group A. Overall, the 5.7 mm × 10 mm combination of implant length and diameter showcased the best performance in both groups. The findings demonstrate that wider implants with a proportional length offer greater resistance to displacement forces. In addition, the use of rigid connection design provides superior biomechanical performance in tooth-implant fixed partial dentures and reduces the risk of micromotion with its associated complications such as ligament overstretching and implant overload, achieving predictable prognosis and enhancing the stability of the protheses. [ABSTRACT FROM AUTHOR]

Introduction: Periodontal disease is a common oral infection which affects the tooth-supportive tissues directly. Considering the limitation of present regenerative treatments for severe periodontal cases, cytotherapies have been gradually introduced. Human periodontal ligament-derived mesenchymal stromal cells (hPDLMSCs), while identified as one of the promising cell sources for periodontal regenerative therapy, still hold some problems in the clinical application especially their limited life span. To solve the problems, human induced pluripotent stem cells (hiPSCs) are taken into consideration as a robust supply for hPDLMSCs. Methods: The induction of hPDLMSCs was performed based on the generation of neural crest-like cells (NCLCs) from hiPSCs. Fibronectin and laminin were tested as coating materials for NCLCs differentiation when following previous protocol, and the characteristics of induced cells were identified by flow cytometry and RT-qPCR for evaluating the induction efficiency. Subsequently, selected dental ectoderm signaling-related cytokines were applied for hPDLMSCs induction for 14 days, and dental mesenchyme-related genes, dental follicle-related genes and hPDL-related genes were tested by RT-qPCR for the evaluation of differentiation. Results: Compared to the 58% in laminin-coated condition, fibronectin-coated condition had a higher induction efficiency of CD271high cells as 86% after 8-day induction, while the mesenchymal potential of induced NCLCs was similar between two coating materials.It was shown that the gene expressions of dental mesenchyme, dental follicles and hPDL cells were significantly enhanced with the stimulation of the combination with fibroblast growth factor 8b (FGF8b), FGF2, and bone morphogenetic protein 4 (BMP4). Conclusion: FN coating was more effective in NCLCs induction, and the FGF8b+FGF2+BMP4 growth factor cocktail was effective in hPDLMSC-like cell generation. These findings underscored the likely regenerative potential of hiPSCs as an applicable and promising curative strategy for periodontal diseases.

Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force–guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell–derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force–activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration. [ABSTRACT FROM AUTHOR]

Introduction: The periodontium is a connective tissue which consists of periodontal ligament, alveolar bone, cementum and gingiva. Periodontal ligament (PDL) is a specialized connective tissue that connects the cementum – coating the surface of the tooth – to the alveolar bone. Mohawk homeobox (Mkx) is a transcription factor that is expressed in PDL, that is known to play a vital role in the development and homeostasis of PDL. A detailed functional analysis of Mkx in the periodontal ligament for alveolar bone and cementum metabolism has not yet been conducted. Materials and methods: Alveolar bone height, bone mineral density (BMD) and bone volume fractions (Bone volume/Total volume: BV/TV) were measured and analyzed using micro-computed tomography (Micro-CT) and 3DBon on 7-week-old male wild-type (WT) (Mkx+/+) (n = 10) and Mkx-knockout (Mkx−/−) (n = 6) rats. Hematoxylin and Eosin (H&E), tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP) and Masson Trichrome staining were performed on 5, 6, and 7-week-old Mkx+/+ and Mkx−/− rats. Cementum surface area and the number of TRAP-positive osteoclasts/mm were quantified, measured, and compared for 5,6 and 7-week-old Mkx+/+ and Mkx−/− rats (n = 3 each). Results: The level of alveolar bone height was significantly higher in Mkx−/− rats than in Mkx+/+ rats. On the other hand, there was significantly less BMD in Mkx−/− alveolar bone. A significant increase in cellular cementum could be observed as early as 5 weeks in Mkx−/− rats when compared with Mkx+/+ rats of the same age. More TRAP-positive osteoclasts were observed in Mkx−/− rats. Conclusion: Our findings further reveal the essential roles of Mkx in the homeostasis of the periodontal tissue. Mkx was found to contribute to bone and cementum metabolism and may be essential to the prevention of diseases such as periodontitis, and could show potential in regenerative treatments.

Featured Application: For a clinician, knowing the amounts of load that can be safely applied during a periodontal breakdown helps in improving the predictability of the orthodontic treatment and avoiding the ischemic and resorptive risks. Thus, knowing that an intact periodontium can bear up to 2.4 N without major ischemic or resorptive risks is of extreme importance. The 4 mm breakdown reference point, after which the applied loads should be lower than 1 N, supplies valuable data for both orthodontics and periodontology. The stress distribution areas displayed for each movement and bone loss level create a general complete image of PDL biomechanical behavior. For a researcher, providing a way to gain the much-needed results for dental studies with an accuracy comparable with those provided by the engineering field is valuable, since FEA is the only available method that allows the individual study of each dental tissue's component, and the current numerical studies have produced debatable and sometimes contradictory results. Thus, by employing the ductile resemblance material type failure criteria (T and VM) and linear elasticity, isotropy, and homogeneity/non-homogeneity as boundary condition assumptions in the study of PDL, the present study obtained results that are in agreement with clinical knowledge. Moreover, the above-mentioned boundary conditions are correct, up to an applied load of 2.4 N (with up to 1 N being acknowledged as mechanically correct). (1) Background: Herein, finite element analysis (FEA) of the periodontal ligament (PDL) was used to assess differences between Tresca (T-non-homogenous) and Von Mises (VM-homogenous) criterion, by simulating a 0–8 mm periodontal breakdown under five orthodontic movements (extrusion, intrusion, rotation, tipping, and translation) and three loads (0.6, 1.2, and 2.4 N). Additionally, we addressed the issues of proper boundary condition selection for more than 1 N loads and correlated the results with the maximum hydrostatic pressure (MHP) and available knowledge, evaluating ischemic and resorptive risks for more than 1 N orthodontic loads. (2) Methods: Eighty-one models of the second lower premolar (nine patients) with intact and 1–8 mm reduced periodontia were created. The assumed boundary conditions were isotropy, homogeneity, and linear elasticity. A total of 486 FEA simulations were performed in Abaqus. (3) Results: Both criteria displayed similar qualitative results, with T being quantitatively 15% higher and better suited. The assumed boundary conditions seem to be correct up to 2.4 N of the applied load. (4) Conclusions: Both criteria displayed constant deformations and displacements manifested in the same areas independently of the load's amount, the only difference being their intensity (doubling—1.2 N; quadrupling—2.4 N). Moreover, 2.4 N seems safe for intact periodontium, while, after a 4 mm loss (seen as the reference point), a load of more than 1 N seems to have significant ischemic and resorptive risks. [ABSTRACT FROM AUTHOR]

The literature presents insufficient data evaluating the displacement and micromotion effects resulting from the combined use of tooth-implant connections in fixed partial dentures. Analyzing the biomechanical behavior of tooth-implant fixed partial denture (FPD) prothesis is vital for achieving an optimum design and successful clinical implementation. The objective of this study was to determine the relative significance of connector design on the displacement and micromotion of tooth-implant-supported fixed dental prostheses under occlusal vertical loading. A unilateral Kennedy class I mandibular model was created using a 3D reconstruction from CT scan data. Eight simulated designs of tooth-implant fixed partial dentures (FPDs) were split into two groups: Group A with rigid connectors and Group B with non-rigid connectors. The models were subjected to a uniform vertical load of 100 N. Displacement, strain, and stress were computed using finite element analysis. The materials were defined as isotropic, homogeneous, and exhibiting linear elastic properties. This study focused on assessing the maximum displacement in various components, including the bridge, mandible, dentin, cementum, periodontal ligament (PDL), and implant. Displacement values were predominantly higher in Group B (non-rigid) compared to Group A (rigid) in all measured components of the tooth-implant FPDs. Accordingly, a statistically significant difference was observed between the two groups at the FPD bridge (p value = 0.021 *), mandible (p value = 0.021 *), dentin (p value = 0.043 *), cementum (p value = 0.043 *), and PDL (p value = 0.043 *). Meanwhile, there was an insignificant increase in displacement values recorded in the distal implant (p value = 0.083). This study highlighted the importance of connector design in the overall stability and performance of the prosthesis. Notably, the 4.7 mm × 10 mm implant in Group B showed a displacement nearly 92 times higher than its rigid counterpart in Group A. Overall, the 5.7 mm × 10 mm combination of implant length and diameter showcased the best performance in both groups. The findings demonstrate that wider implants with a proportional length offer greater resistance to displacement forces. In addition, the use of rigid connection design provides superior biomechanical performance in tooth-implant fixed partial dentures and reduces the risk of micromotion with its associated complications such as ligament overstretching and implant overload, achieving predictable prognosis and enhancing the stability of the protheses.

Background: Periodontitis is a long-term, multifactorial inflammatory condition that is triggered by bacterial germs and interacts with the host's immune system. The unique attachment of fibrous tissue between the cementum and bone presents a challenge for periodontal regeneration. Aim: To achieve the lowest optimum dose of BMP-7 that helps in periodontal regeneration, involving newly formed cementum, PDL and bone Materials and methods: Five healthy mongrel dogs were used for the study. A critical class III furcation defect was created using rotating burs. The bone defects (ten defects for each group) were allocated to one of the subsequent groups: (Group 1) control with the surgical defect only. (Group 2) Surgical defect implanted with hydrogel only (CS/β-GP). (Group 3) Surgical defect implanted with CS/BMP-7 (50 ng/ml). (Group 4) Surgical defect implanted with CS/BMP-7 (100 ng/ml). Results: Histomorphometric and H&E analysis revealed a statistically significant difference in bone, PDL, and cementum regeneration defects filled with CS/BMP-7 (100 ng/ml) compared with other groups. Conclusion: The standard effective dose for BMP-7 use in periodontal regeneration is 100 ng/ml.

Objective: The three-dimensional morphological structures of periodontal ligaments (PDLs) are important data for periodontal, orthodontic, prosthodontic, and implant interventions. This study aimed to employ a deep learning (DL) algorithm to segment the PDL automatically in cone-beam computed tomography (CBCT). Method: This was a retrospective study. We randomly selected 389 patients and 1734 axial CBCT images from the CBCT database, and designed a fully automatic PDL segmentation computer-aided model based on instance segmentation Mask R-CNN network. The labels of the model training were ‘teeth’ and ‘alveolar bone’, and the ‘PDL’ is defined as the region where the ‘teeth’ and ‘alveolar bone’ overlap. The model’s segmentation performance was evaluated using CBCT data from eight patients outside the database. Results: Qualitative evaluation indicates that the PDL segmentation accuracy of incisors, canines, premolars, wisdom teeth, and implants reached 100%. The segmentation accuracy of molars was 96.4%. Quantitative evaluation indicates that the mIoU and mDSC of PDL segmentation were 0.667 ± 0.015 (>0.6) and 0.799 ± 0.015 (>0.7) respectively. Conclusion: This study analysed a unique approach to AI-driven automatic segmentation of PDLs on CBCT imaging, possibly enabling chair-side measurements of PDLs to facilitate periodontists, orthodontists, prosthodontists, and implantologists in more efficient and accurate diagnosis and treatment planning.

Periodontitis is a long-term, multifactorial inflammatory condition that is triggered by bacterial germs and interacts with the host's immune system. The unique attachment of fibrous tissue between the cementum and bone presents a challenge for periodontal regeneration. To achieve the lowest optimum dose of BMP-7 that helps in periodontal regeneration, involving newly formed cementum, PDL and bone Five healthy mongrel dogs were used for the study. A critical class III furcation defect was created using rotating burs. The bone defects (ten defects for each group) were allocated to one of the subsequent groups: (Group 1) control with the surgical defect only. (Group 2) Surgical defect implanted with hydrogel only (CS/β-GP). (Group 3) Surgical defect implanted with CS/BMP-7 (50 ng/ml). (Group 4) Surgical defect implanted with CS/BMP-7 (100 ng/ml). Histomorphometric and H&E analysis revealed a statistically significant difference in bone, PDL, and cementum regeneration defects filled with CS/BMP-7 (100 ng/ml) compared with other groups. The standard effective dose for BMP-7 use in periodontal regeneration is 100 ng/ml. [ABSTRACT FROM AUTHOR]

(1) Background: Herein, finite element analysis (FEA) of the periodontal ligament (PDL) was used to assess differences between Tresca (T-non-homogenous) and Von Mises (VM-homogenous) criterion, by simulating a 0–8 mm periodontal breakdown under five orthodontic movements (extrusion, intrusion, rotation, tipping, and translation) and three loads (0.6, 1.2, and 2.4 N). Additionally, we addressed the issues of proper boundary condition selection for more than 1 N loads and correlated the results with the maximum hydrostatic pressure (MHP) and available knowledge, evaluating ischemic and resorptive risks for more than 1 N orthodontic loads. (2) Methods: Eighty-one models of the second lower premolar (nine patients) with intact and 1–8 mm reduced periodontia were created. The assumed boundary conditions were isotropy, homogeneity, and linear elasticity. A total of 486 FEA simulations were performed in Abaqus. (3) Results: Both criteria displayed similar qualitative results, with T being quantitatively 15% higher and better suited. The assumed boundary conditions seem to be correct up to 2.4 N of the applied load. (4) Conclusions: Both criteria displayed constant deformations and displacements manifested in the same areas independently of the load’s amount, the only difference being their intensity (doubling—1.2 N; quadrupling—2.4 N). Moreover, 2.4 N seems safe for intact periodontium, while, after a 4 mm loss (seen as the reference point), a load of more than 1 N seems to have significant ischemic and resorptive risks.

Background and Objective: Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage‐inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis in femur. However, the role of DDIT3 in periodontitis has not been elucidated. This research aimed to explore the role and mechanisms of DDIT3 in periodontitis. Methods: DDIT3 gene knockout (KO) mice were generated using a CRISPR/Cas9 system. Experimental periodontitis models were established to explore the role of DDIT3 in periodontitis. The expression of DDIT3 in periodontal tissues was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemistry (IHC). The alveolar bone phenotypes were observed by micro‐CT and stereomicroscopy. The inflammation levels and osteoclast activity were examined by histological staining, immunostaining, and qRT‐PCR. Bone marrow‐derived macrophages (BMMs) were isolated to confirm the effects of DDIT3 on osteoclast formation and function in vitro. Results: The increased expression of DDIT3 in murine inflamed periodontal tissues was detected. DDIT3 knockout aggravated alveolar bone loss and enhanced expression levels of inflammatory cytokines in murine periodontitis models. Increased osteoclast formation and higher expression levels of osteoclast‐specific markers were observed in the inflamed periodontal tissues of KO mice. In vitro, DDIT3 deficiency promoted the formation of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated osteoclasts and the bone resorption activity of mature osteoclasts. Conclusions: Our results demonstrate that DDIT3 deletion aggravated alveolar bone loss in experimental periodontitis through enhanced inflammatory reactions and osteoclastogenesis. The anti‐inflammation and the inhibition of bone loss by DDIT3 in murine periodontitis provides a potential novel therapeutic strategy for periodontitis. [ABSTRACT FROM AUTHOR]

Orthodontic tooth movement is of interest to both the medical and the engineering communities. Recent studies focused their attention mainly on the stress distribution within the periodontal ligament and the surrounding alveolar bone prior to the remodeling stage. Yet, although motion is indeed triggered by the exerted stress distribution, these remodeling processes are the main driver for significant (and permanent) tooth movements. Other studies attempted to provide such a holistic mechanical model for both the stress distribution and the remodeling processes to describe the movement of the tooth along an orthodontic treatment. Nevertheless, these methods are cumbersome and slow to run, and therefore, are unlikely to provide a clinical decision support platform. This paper aims to bridge this gap by providing a relaxed, simplified numerical model. The scheme is described, and its limitations and main assumptions are stated. The model is then optimized to accommodate clinical accuracy needs. Lastly, validation is provided by comparing the model to a recent study, which demonstrates the good agreement between the model and actual real-world clinical cases. [ABSTRACT FROM AUTHOR]

Abstract Management of avulsed teeth after replantation often leads to an unfavorable outcome. Damage to the thin and vulnerable periodontal ligament is the key reason for failure. Cell- or stem cell-based regenerative medicine has emerged in the past two decades as a promising clinical treatment modality to improve treatment outcomes. This concept has also been tested for the management of avulsed teeth in animal models. This review focuses on the discussion of limitation of current management protocols for avulsed teeth, cell-based therapy for periodontal ligament (PDL) regeneration in small and large animals, the challenges of de novo regeneration of PDL on denuded root in the edentulous region using a mini-swine model, and establishing a prospective new clinical protocol to manage avulsed teeth based on the current progress of cell-based PDL regeneration studies.

Background and Aims: Survival of periodontal ligament (PDL) cells after avulsion is an important factor in treatment prognosis. Grapefruit Seed Extract (GSE) can be a proper environment for preserving periodontal ligament cells. The objective of this study was to analyze the effect of different concentrations of GSE on the proliferation of fibroblast PDL cells. Materials and Methods: In this study, the undifferentiated PDL fibroblasts were obtained from two human premolars teeth and cultured in Dulbecco’s modified Eagle’s medium (DMEM). The cultured cells were exposed to different concentrations of GSE. The positive and negative control groups were cultured in fetal bovine serum (FBS) 10% and in a medium without FBS 10%, respectively. The plates were incubated for 1, 6, 12, 24, and 48 hrs. The PDL cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Statistical analysis of data was accomplished using repeated measure ANOVA with Post HOC Tukey, P0.05). Furthermore, all the samples were similar to the positive control group in three of the five timeperiods (P>0.05). Conclusion: GSE was more effective in fewer concentration and longer periods and it had no toxic effect on PDL cells. Therefore, GSE can be considred as a promoting medium in PDL regeneration of avulsed permanent teeth in the future.

Orthodontic tooth movement is of interest to both the medical and the engineering communities. Recent studies focused their attention mainly on the stress distribution within the periodontal ligament and the surrounding alveolar bone prior to the remodeling stage. Yet, although motion is indeed triggered by the exerted stress distribution, these remodeling processes are the main driver for significant (and permanent) tooth movements. Other studies attempted to provide such a holistic mechanical model for both the stress distribution and the remodeling processes to describe the movement of the tooth along an orthodontic treatment. Nevertheless, these methods are cumbersome and slow to run, and therefore, are unlikely to provide a clinical decision support platform. This paper aims to bridge this gap by providing a relaxed, simplified numerical model. The scheme is described, and its limitations and main assumptions are stated. The model is then optimized to accommodate clinical accuracy needs. Lastly, validation is provided by comparing the model to a recent study, which demonstrates the good agreement between the model and actual real-world clinical cases.

Introduction: The functional interplay between cementum of the root and alveolar bone of the socket is tuned by a uniquely positioned 70–80 µm wide fibrous and lubricious ligament in a dentoalveolar joint (DAJ). In this study, structural and biomechanical properties of the DAJ, periodontal ligament space (PDL‐space also known as the joint space), alveolar bone of the socket, and cementum of the tooth root that govern the biomechanics of a lipopolysaccharide (LPS)‐affected DAJ were mapped both in space and time. Methods: The hemi‐maxillae from 20 rats (4 control at 6 weeks of age, 4 control and 4 LPS‐affected at 12 weeks of age, 4 control and 4 LPS‐affected at 16 weeks of age) were investigated using a hybrid technique; micro‐X‐ray computed tomography (5 µm resolution) in combination with biomechanical testing in situ. Temporal variations in bone and cementum volume fractions were evaluated. Trends in mineral apposition rates (MAR) in additional six Sprague Dawley rats (3 controls, 3 LPS‐affected) were revealed by transforming spatial fluorochrome signals to functional growth rates (linearity factor ‐ RW) of bone, dentin, and cementum using a fast Fourier transform on fluorochrome signals from 100‐µm hemi‐maxillae sections. Results: An overall change in LPS‐affected DAJ biomechanics (a 2.5–4.5X increase in tooth displacement and 2X tooth rotation at 6 weeks, no increase in displacement and a 7X increase in rotation at 12 weeks; 27% increase in bone effective strain at 6 weeks and 11% at 12 weeks relative to control) was associated with structural changes in the coronal regions of the DAJ (15% increase in PDL‐space from 0 to 6 weeks but only 5% from 6 to 12 weeks compared to control). A significant increase (p < 0.05) in PDL‐space between ligated and age‐matched control was observed. The bone fraction of ligated at 12 weeks was significantly lower than its age‐matched control, and no significant differences (p > 0.05) between groups were observed at 6 weeks. Cementum in the apical regions grew faster but nonlinearly (11% and 20% increase in cementum fraction (CF) at 6 and 12 weeks) compared to control. Alveolar bone revealed site‐specific nonlinear growth with an overall increase in MAR (108.5 µm/week to 126.7 µm/week after LPS treatment) compared to dentin (28.3 µm/week in control vs. 26.1 µm/week in LPS‐affected) and cementum (126.5 µm/week in control vs. 119.9 µm/week in LPS‐affected). A significant increase in CF (p < 0.05) in ligated specimens was observed at 6 weeks of age. Conclusions: Anatomy‐specific responses of cementum and bone to the mechano‐chemo stimuli, and their collective temporal contribution to observed changes in PDL‐space were perpetuated by altered tooth movement. Data highlight the "resilience" of DAJ function through the predominance of nonlinear growth response of cementum, changes in PDL‐space, and bone architecture. Despite the significant differences in bone and cementum architectures, data provided insights into the reactionary effects of cementum as a built‐in compensatory mechanism to reestablish functional competence of the DAJ. The spatial shifts in architectures of alveolar bone and cementum, and consequently ligament space, highlight adaptations farther away from the site of insult, which also is another novel insight from this study. These adaptations when correlated within the context of joint function (biomechanics) illustrate that they are indeed necessary to sustain DAJ function albeit being pathological. [ABSTRACT FROM AUTHOR]

Management of avulsed teeth after replantation often leads to an unfavorable outcome. Damage to the thin and vulnerable periodontal ligament is the key reason for failure. Cell- or stem cell-based regenerative medicine has emerged in the past two decades as a promising clinical treatment modality to improve treatment outcomes. This concept has also been tested for the management of avulsed teeth in animal models. This review focuses on the discussion of limitation of current management protocols for avulsed teeth, cell-based therapy for periodontal ligament (PDL) regeneration in small and large animals, the challenges of de novo regeneration of PDL on denuded root in the edentulous region using a mini-swine model, and establishing a prospective new clinical protocol to manage avulsed teeth based on the current progress of cell-based PDL regeneration studies. [ABSTRACT FROM AUTHOR]

The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro-computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume after 9 wk of Wnt1 expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of Wnt1 expression. However, 9 wk of Wnt1 expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of Wnt1 expression revealed that Wnt1 expression affects mandibular bone and growing incisors but not molar teeth, indicating that Wnt1 influences only growing tissues. To further investigate the effect of Wnt1 on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing Wnt1-HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that Wnt1 promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, Wnt1 as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry. [ABSTRACT FROM AUTHOR]

Introduction: Periodontal disease is a common oral infection which affects the tooth-supportive tissues directly. Considering the limitation of present regenerative treatments for severe periodontal cases, cytotherapies have been gradually introduced. Human periodontal ligament-derived mesenchymal stromal cells (hPDLMSCs), while identified as one of the promising cell sources for periodontal regenerative therapy, still hold some problems in the clinical application especially their limited life span. To solve the problems, human induced pluripotent stem cells (hiPSCs) are taken into consideration as a robust supply for hPDLMSCs., Methods: The induction of hPDLMSCs was performed based on the generation of neural crest-like cells (NCLCs) from hiPSCs. Fibronectin and laminin were tested as coating materials for NCLCs differentiation when following previous protocol, and the characteristics of induced cells were identified by flow cytometry and RT-qPCR for evaluating the induction efficiency. Subsequently, selected dental ectoderm signaling-related cytokines were applied for hPDLMSCs induction for 14 days, and dental mesenchyme-related genes, dental follicle-related genes and hPDL-related genes were tested by RT-qPCR for the evaluation of differentiation., Results: Compared to the 58% in laminin-coated condition, fibronectin-coated condition had a higher induction efficiency of CD271 high cells as 86% after 8-day induction, while the mesenchymal potential of induced NCLCs was similar between two coating materials.It was shown that the gene expressions of dental mesenchyme, dental follicles and hPDL cells were significantly enhanced with the stimulation of the combination with fibroblast growth factor 8b (FGF8b), FGF2, and bone morphogenetic protein 4 (BMP4)., Conclusion: FN coating was more effective in NCLCs induction, and the FGF8b+FGF2+BMP4 growth factor cocktail was effective in hPDLMSC-like cell generation. These findings underscored the likely regenerative potential of hiPSCs as an applicable and promising curative strategy for periodontal diseases., (© 2024 The Author(s).)

Background and Aims: Survival of periodontal ligament (PDL) cells after avulsion is an important factor in treatment prognosis. Grapefruit Seed Extract (GSE) can be a proper environment for preserving periodontal ligament cells. The objective of this study was to analyze the effect of different concentrations of GSE on the proliferation of fibroblast PDL cells. Materials and Methods: In this study, the undifferentiated PDL fibroblasts were obtained from two human premolars teeth and cultured in Dulbecco’s modified Eagle’s medium (DMEM). The cultured cells were exposed to different concentrations of GSE. The positive and negative control groups were cultured in fetal bovine serum (FBS) 10% and in a medium without FBS 10%, respectively. The plates were incubated for 1, 6, 12, 24, and 48 hrs. The PDL cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Statistical analysis of data was accomplished using repeated measure ANOVA with Post HOC Tukey, P<0.05 was considered statistically significant. Results: We found out that among different concentrations of GSE, 1:128 had the most impact on undifferentiated PDL fibroblasts. Although, the cell vitality was higher in the twelfth hour, 1:128 GSE and in the forty-eighth hour, 1:1024 GSE than the positive control group but they were not statistically significant (P>0.05). Furthermore, all the samples were similar to the positive control group in three of the five timeperiods (P>0.05). Conclusion: GSE was more effective in fewer concentration and longer periods and it had no toxic effect on PDL cells. Therefore, GSE can be considred as a promoting medium in PDL regeneration of avulsed permanent teeth in the future. [ABSTRACT FROM AUTHOR]

To investigate the role of NF-κB in osteoblast lineage cells and periodontal ligament (PDL) fibroblasts during orthodontic tooth movement (OTM). Transgenic mice that expressed a dominant negative mutant of the inhibitor of kB kinase (IKK-DN) with lineage specific expression in osteoblastic cells and PDL fibroblasts driven by a response element in the collagen1α1 promoter and matched wild-type (WT) mice were examined. A 10-12 g force was applied by a NiTi coil and maintained for 5 or 12 days. OTM distance, PDL width, and bone volume fraction were measured using micro computed tomography. Osteoclast numbers were counted in tartrate-resistant acid phosphatase-stained sections. Activation of nuclear factor kappa B (NF-kB) was assessed by nuclear localization of p65, and the receptor activator of nuclear factor-κB ligand (RANKL) was measured by immunofluorescence and compared to control specimens with no orthodontic force. OTM-induced NF-kB activation (p65 nuclear localization) in WT mice was largely blocked in transgenic (TG) mice. OTM was significantly reduced in the TG mice compared to WT mice along with reduced osteoclastogenesis, narrower PDL width, higher bone volume fraction, and reduced RANKL expression. Osteoblast lineage cells and PDL fibroblasts are key contributors to alveolar bone remodeling in OTM through IKKβ dependent NF-κB activation. [ABSTRACT FROM AUTHOR]

The periodontal ligaments (PDLs) with specific orientations to tooth-root surfaces play a key role in generating biomechanical responses between the alveolar bone and cementum as a tooth-supporting tissue. However, control of angulations and regeneration of the ligamentous tissues within micron-scaled interfaces remains challenging. To overcome this limitation, this study investigated surface fabrications with microgroove patterns to control orientations of rat PDL cells in vitro and fibrous tissues in vivo. After being harvested, rat PDL cells were cultured and three different microgroove patterns (∠PDL groove = 0°, ∠PDL groove = 45°, and ∠PDL groove = 90°) were created by the digital slicing step in 3D printing. Cell-seeded scaffolds were subcutaneously transplanted at 3 and 6 weeks. In histology images, rat PDL cells were spatially controlled to angularly organize following the microgroove patterns and fibrous tissues were formed in scaffolds with specific angulations, which were reflected by additively manufactured microgroove topographies. Based on the results, specifically characterized surface topographies were significant to directly/indirectly organizing rat PDL cell alignments and fibrous tissue orientations. Therefore, interactions between surface topographies and tissue organizations could be one of the key moderators for the multiple tissue complex (bone-ligament-cementum) neogenesis in periodontal tissue engineering. [ABSTRACT FROM AUTHOR]

The periodontal complex consists of the periodontal ligament (PDL), alveolar bone, and cementum, which work together to turn mechanical load into biological responses that are responsible for maintaining a homeostatic environment. However oral microbes, under conditions of dysbiosis, may challenge the actin dynamic properties of the PDL in the context of periodontal disease. To study this process, we examined host-microbial interactions in the context of the periodontium via molecular and functional cell assays and showed that human PDL cell interactions with Treponema denticola induce actin depolymerization through a novel actin reorganization signaling mechanism. This actin reorganization mechanism and loss of cell adhesion is a pathological response characterized by an initial upregulation of RASA4 mRNA expression resulting in an increase in matrix metalloproteinase-2 activity. This mechanism is specific to the T. denticola effector protein, dentilisin, thereby uncovering a novel effect for Treponema denticola-mediated RASA4 transcriptional activation and actin depolymerization in primary human PDL cells.

The periodontal complex consists of the periodontal ligament (PDL), alveolar bone, and cementum, which work together to turn mechanical load into biological responses that are responsible for maintaining a homeostatic environment. However oral microbes, under conditions of dysbiosis, may challenge the actin dynamic properties of the PDL in the context of periodontal disease. To study this process, we examined host-microbial interactions in the context of the periodontium via molecular and functional cell assays and showed that human PDL cell interactions with Treponema denticola induce actin depolymerization through a novel actin reorganization signaling mechanism. This actin reorganization mechanism and loss of cell adhesion is a pathological response characterized by an initial upregulation of RASA4 mRNA expression resulting in an increase in matrix metalloproteinase-2 activity. This mechanism is specific to the T. denticola effector protein, dentilisin, thereby uncovering a novel effect for Treponema denticola -mediated RASA4 transcriptional activation and actin depolymerization in primary human PDL cells. [ABSTRACT FROM AUTHOR]

The paper is concerned with simulation of the periodontal ligament response to force in the initial phase of orthodontic tooth movement. This is based on two previous investigations, a in vitro experiment with specimens of porcine mandibular premolars and a in vivo experiment on human upper first incisors. For the curve fit of the in vitro experiment a model function, assuming viscoelasticity, was introduced. The viscoelastic model function was augmented by a ramp rise time term, to account for observed dependence of the response on actuator velocity, and a previous load history term, to account for the effect of the previous tests on the current test. The correlation coefficient of a curve fit for all tests grouped together was R 2 = 0.98. Next, a curve fit of the in vivo experiment was done. Good correlation was found for a simplified model function, without viscoelastic term ( R 2 = 0.96 ). For both tests, in vitro and in vivo, the ramp rise time term improved correlation. A finite element model of the specimen of the in vitro experiment was created. For the PDL a hyperelastic constitutive model for compressible material was used and model parameters were identified. The present work indicates that the macroscopic response of the periodontal ligament to an external load can be simulated with a poro-visco-hyperelastic model. The simulation showed that poroelastic behaviour will gradually cease when viscoelastic relaxation progresses. This followed also from dimensionless analysis. As a consequence, for slow loading, or if initial response to fast loading is not of interest, a visco-hyperelastic model may suffice. To identify parameters of the finite element model several optimisation problems were solved. A model function, which can be regarded as a reduced order model, allowed a full factorial experiment (analysis) at low cost, to identify initial parameters. The thus found parameters were further refined with an optimum interpolation meta-model. That is, for limited number of parameter combinations the response was simulated with the finite element model and a refined parameter study was conducted by means of optimal interpolation. The thus found optimal parameters were verified by simulation with the finite element model. Optimal interpolation is computationally cheap, which allowed full factorial experiments at low cost. [ABSTRACT FROM AUTHOR]

Periodontal disease is characterized by the destruction of the hard and soft tissues comprising the periodontium. This destruction translates to a degradation of the extracellular matrices (ECM), mediated by bacterial proteases, host-derived matrix metalloproteinases (MMPs), and other proteases released by host tissues and immune cells. Bacterial pathogens interact with host tissue, triggering adverse cellular functions, including a heightened immune response, tissue destruction, and tissue migration. The oral spirochete Treponema denticola is highly associated with periodontal disease. Dentilisin, a T. denticola outer membrane protein complex, contributes to the chronic activation of pro-MMP-2 in periodontal ligament (PDL) cells and triggers increased expression levels of activators and effectors of active MMP-2 in PDL cells. Despite these advances, no mechanism for dentilisin-induced MMP-2 activation or PDL cytopathic behaviors leading to disease is known. Here, we describe a method for purification of large amounts of the dentilisin protease complex from T. denticola and demonstrate its ability to activate MMP-2, a key regulator of periodontal tissue homeostasis. The T. denticola dentilisin and MMP-2 activation model presented here may provide new insights into the dentilisin protein and identify potential therapeutic targets for further research. Key features • This protocol builds upon a method described by Cunningham et al. [1] for selective release of Treponema outer membrane proteins. • We adapted the protocol for the purification of biologically active, detergent-stable outer membrane protein complexes from large batch cultures of T. denticola . • The protocol involves large-scale preparative electrophoresis using a Model 491 Prep Cell. • We then use gelatin zymography to demonstrate the activity of the purified dentilisin complex by its ability to activate matrix metalloproteinase 2 (MMP-2)., Competing Interests: Competing interestsThe authors declare no conflict of interest., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Periodontal tissue engineering is a possible strategy for regeneration of human periodontal ligaments (PDLs) around dental implants. The aim of this study was to investigate the feasibility of three-dimensional polyglycolic acid (PGA) fibre mesh as a scaffold for human PDL cells in periodontal tissue engineering with a nude mouse model. Human PDL cells at a density of 2 × 107/mL were seeded onto porous PGA scaffolds. After seven days of incubation in vitro, the PGA–cell constructs and cell-free scaffolds were subcutaneously implanted on the back of BALB/c-nu mice bilaterally. The mice were sacrificed in batches at 2, 4, 6 and 8 weeks after implantation, and the harvests were examined histologically. In our study, PGA scaffolds promoted mRNA expression of collagen type I, collagen type III and fibronectin in PDL cells. Masson's trichrome staining showed that after two weeks, the implants were well vascularised in vivo. Fluorescence microscopy indicated that the newly formed tissues were derived from the GFP-labelled human PDL cells. Our study suggested that the delivery of PDL cells via a non-woven PGA mesh might serve as a viable approach to promote periodontal tissue regeneration.

Tooth eruption is a complex process requiring precise interaction between teeth and adjacent tissues. Molecular analysis demonstrates that bone remodeling plays an essential role during eruption, suggesting that a parathyroid hormone 1 receptor (PTH1R) gene mutation is associated with disturbances in bone remodeling and results in primary failure of eruption (PFE). Recent research reveals the function of PTH1R signaling in mesenchymal progenitors, whereas the function of PTH1R in mesenchymal stem cells during tooth eruption remains incompletely understood. We investigated the specific role of PTH1R in Prx1+ progenitor expression during eruption. We found that Prx1+-progenitors occur in mesenchymal stem cells residing in alveolar bone marrow surrounding incisors, at the base of molars and in the dental follicle and pulp of incisors. Mice with conditional deletion of PTH1R using the Prx1 promoter exhibited arrested mandibular incisor eruption and delayed molar eruption. Micro-computed tomography, histomorphometry, and molecular analyses revealed that mutant mice had significantly reduced alveolar bone formation concomitant with downregulated gene expression of key regulators of osteogenesis in PTH1R-deficient cells. Moreover, culturing orofacial bone-marrow-derived mesenchymal stem cells (OMSCs) from Prx1Cre;PTH1Rfl/fl mice or from transfecting Cre recombinase adenovirus in OMSCs from PTH1Rfl/fl mice suggested that lack of Pth1r expression inhibited osteogenic differentiation in vitro. However, bone resorption was not affected by PTH1R ablation, indicating the observed reduced alveolar bone volume was mainly due to impaired bone formation. Furthermore, we found irregular periodontal ligaments and reduced Periostin expression in mutant incisors, implying loss of PTH1R results in aberrant differentiation of periodontal ligament cells. Collectively, these data suggest that PTH1R signaling in Prx1+ progenitors plays a critical role in alveolar bone formation and periodontal ligament development during eruption. These findings have implications for our understanding of the physiologic and pathologic function of PTH1R signaling in tooth eruption and the progression of PFE. [ABSTRACT FROM AUTHOR]

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The periodontal ligaments (PDLs) with specific orientations to tooth-root surfaces play a key role in generating biomechanical responses between the alveolar bone and cementum as a tooth-supporting tissue. However, control of angulations and regeneration of the ligamentous tissues within micron-scaled interfaces remains challenging. To overcome this limitation, this study investigated surface fabrications with microgroove patterns to control orientations of rat PDL cells in vitro and fibrous tissues in vivo. After being harvested, rat PDL cells were cultured and three different microgroove patterns (∠PDL groove = 0°, ∠PDL groove = 45°, and ∠PDL groove = 90°) were created by the digital slicing step in 3D printing. Cell-seeded scaffolds were subcutaneously transplanted at 3 and 6 weeks. In histology images, rat PDL cells were spatially controlled to angularly organize following the microgroove patterns and fibrous tissues were formed in scaffolds with specific angulations, which were reflected by additively manufactured microgroove topographies. Based on the results, specifically characterized surface topographies were significant to directly/indirectly organizing rat PDL cell alignments and fibrous tissue orientations. Therefore, interactions between surface topographies and tissue organizations could be one of the key moderators for the multiple tissue complex (bone-ligament-cementum) neogenesis in periodontal tissue engineering.

Objective: The three-dimensional morphological structures of periodontal ligaments (PDLs) are important data for periodontal, orthodontic, prosthodontic, and implant interventions. This study aimed to employ a deep learning (DL) algorithm to segment the PDL automatically in cone-beam computed tomography (CBCT)., Method: This was a retrospective study. We randomly selected 389 patients and 1734 axial CBCT images from the CBCT database, and designed a fully automatic PDL segmentation computer-aided model based on instance segmentation Mask R-CNN network. The labels of the model training were 'teeth' and 'alveolar bone', and the 'PDL' is defined as the region where the 'teeth' and 'alveolar bone' overlap. The model's segmentation performance was evaluated using CBCT data from eight patients outside the database., Results: Qualitative evaluation indicates that the PDL segmentation accuracy of incisors, canines, premolars, wisdom teeth, and implants reached 100%. The segmentation accuracy of molars was 96.4%. Quantitative evaluation indicates that the mIoU and mDSC of PDL segmentation were 0.667 ± 0.015 (>0.6) and 0.799 ± 0.015 (>0.7) respectively., Conclusion: This study analysed a unique approach to AI-driven automatic segmentation of PDLs on CBCT imaging, possibly enabling chair-side measurements of PDLs to facilitate periodontists, orthodontists, prosthodontists, and implantologists in more efficient and accurate diagnosis and treatment planning., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xiaofeng Huang reports financial support was provided by This work was supported by Clinical Technology Innovation Project of Beijing Hospital Management Center, China (XMLX202132). Xieting Jia reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China, China (No. 82101005)., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: The periodontium is a connective tissue which consists of periodontal ligament, alveolar bone, cementum and gingiva. Periodontal ligament (PDL) is a specialized connective tissue that connects the cementum - coating the surface of the tooth - to the alveolar bone. Mohawk homeobox (Mkx ) is a transcription factor that is expressed in PDL, that is known to play a vital role in the development and homeostasis of PDL. A detailed functional analysis of Mkx in the periodontal ligament for alveolar bone and cementum metabolism has not yet been conducted., Materials and Methods: Alveolar bone height, bone mineral density (BMD) and bone volume fractions (Bone volume/Total volume: BV/TV) were measured and analyzed using micro-computed tomography (Micro-CT) and 3DBon on 7-week-old male wild-type (WT) ( Mkx +/+ ) (n = 10) and Mkx -knockout ( Mkx -/- ) (n = 6) rats. Hematoxylin and Eosin (H&E), tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP) and Masson Trichrome staining were performed on 5, 6, and 7-week-old Mkx +/+ and Mkx -/- rats. Cementum surface area and the number of TRAP-positive osteoclasts/mm were quantified, measured, and compared for 5,6 and 7-week-old Mkx +/+ and Mkx -/- rats (n = 3 each)., Results: The level of alveolar bone height was significantly higher in Mkx -/- rats than in Mkx +/+ rats. On the other hand, there was significantly less BMD in Mkx -/- alveolar bone. A significant increase in cellular cementum could be observed as early as 5 weeks in Mkx -/- rats when compared with Mkx +/+ rats of the same age. More TRAP-positive osteoclasts were observed in Mkx -/- rats., Conclusion: Our findings further reveal the essential roles of Mkx in the homeostasis of the periodontal tissue. Mkx was found to contribute to bone and cementum metabolism and may be essential to the prevention of diseases such as periodontitis, and could show potential in regenerative treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Tooth autotransplantation (TAT) offers a viable biological approach to tooth replacement in children and adolescents. The aim of this study was to evaluate the outcome of the cone-beam computed tomographic (CBCT)-guided TAT compared to the conventional TAT protocol and to assess the 3-dimensional (3D) patterns of healing after CBCT-guided TAT (secondary aim). This study included 100 autotransplanted teeth in 88 patients. Each experimental group consisted of 50 transplants in 44 patients (31 males and 19 females). The mean (SD) age at the time of surgery was 10.7 (1.1) y for the CBCT-guided group. This was 10.6 (1.3) y for the conventional group. The mean (SD) follow-up period was 4.5 (3.1) y (range, 1.1 to 10.4 y). Overall survival rate for the CBCT-guided TAT was 92% with a success rate of 86% compared to an 84% survival rate and a 78% success rate for the conventional group ( P > 0.005). The following measurements were extracted from the 3D analysis: root hard tissue volume (RV), root length (RL), apical foramen area (AFA), and mean and maximum dentin wall thickness (DWT). Overall, the mean (SD) percentage of tissue change was as follows: RV gain by 65.8% (34.6%), RL gain by 37.3% (31.5%), AFA reduction by 91.1% (14.9%), mean DWT increase by 107.9% (67.7%), and maximum DWT increase by 26.5% (40.1%). Principal component analysis (PCA) identified the mean DWT, RV, and maximum DWT as the parameters best describing the tissue change after TAT. Cluster analysis applied to the variables chosen by the PCA classified the CBCT group into 4 distinct clusters (C1 = 37.2%, C2 = 17.1%, C3 = 28.6%, C4 = 17.1%), revealing different patterns of tissue healing after TAT. The CBCT-guided approach increased the predictability of the treatment. The 3D analysis provided insights into the patterns of healing. CBCT-guided TAT could be adopted as an alternative for the conventional approach. (Clinical trial center and ethical board University Hospitals, KU Leuven: S55287; ClinicalTrials.gov Identifier: NCT02464202). [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Our study was conducted on freshly dissected minipig mandibles. • Force-displacement curves of minipig teeth are similar to those obtained for humans and other animals. • In minipig teeth there is a topographic complimentarity between the tooth and underlying bone surfaces. • When loaded the tooth does not have a direct contact with the underlying bone. The intervening periodontal ligament (PDL) is highly compressed and may act as a shock absorber. • The bone in this upper furcation region is unique. Abstract One strategy evolved by teeth to avoid irreversible damage is to move and deform under the loads incurred during mastication. A key component in this regard is the periodontal ligament (PDL). The role of the bone underlying the PDL is less well defined. We study the interplay between the PDL and the underlying alveolar bone when loaded in the minipig. Using an Instron loading device we confirmed that the force-displacement curves of the molars and premolars of relatively fresh minipig intact mandibles are similar to those obtained for humans and other animals. We then used this information to obtain 3D images of the teeth before and after loading the tooth in a microCT such that the load applied is in the third linear part of the force displacement curve. We observed that at many locations there is a complimentary topography of the cementum and alveolar bone surface, strongly suggesting an active interplay between the tooth and the bone during mastication. We also observed that the loaded tooth does not come into direct contact with the underlying bone surface. A highly compressed layer of PDL is present between the tooth and the bone. The structure of the bone in the upper furcation region has a unique appearance with little obvious microstructure, abundant pores that have a large size range and at many locations the bone at the PDL interface has a needle-like shape. We conclude that there is a close interaction between the tooth, the PDL and the underlying alveolar bone during mastication. The highly compressed PDL layer that separates the tooth from the bone may fulfill a key shock absorbing function. [ABSTRACT FROM AUTHOR]

Periodontal tissue engineering is a possible strategy for regeneration of human periodontal ligaments (PDLs) around dental implants. The aim of this study was to investigate the feasibility of three-dimensional polyglycolic acid (PGA) fibre mesh as a scaffold for human PDL cells in periodontal tissue engineering with a nude mouse model. Human PDL cells at a density of 2 × 107/mL were seeded onto porous PGA scaffolds. After seven days of incubation in vitro, the PGA-cell constructs and cell-free scaffolds were subcutaneously implanted on the back of BALB/c-nu mice bilaterally. The mice were sacrificed in batches at 2, 4, 6 and 8 weeks after implantation, and the harvests were examined histologically. In our study, PGA scaffolds promoted mRNA expression of collagen type I, collagen type III and fibronectin in PDL cells. Masson's trichrome staining showed that after two weeks, the implants were well vascularised in vivo. Fluorescence microscopy indicated that the newly formed tissues were derived from the GFP-labelled human PDL cells. Our study suggested that the delivery of PDL cells via a non-woven PGA mesh might serve as a viable approach to promote periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Background/purpose: Bioaggregates such as Portland cement (PC) can be an economical alternative for mineral trioxide aggregate (MTA) with additional benefit of less discoloration. MTA has been known to induce differentiations of several dental cells. MicroRNAs are important regulators of biological processes, including differentiation, physiologic homeostasis, and disease progression. This study is to explore how PC enhances the differentiation of periodontal ligament (PDL) cells in microRNAs level.Methods: PDL cells were cultured in a regular PC- or MTA-conditioned medium or an osteoinduction medium (OIM). Alizarin red staining was used to evaluate the extent of mineralization. Transfection of microRNA mimics induced exogenous miR-31 and miR-146a expression. The expression of microRNAs and differentiation markers was assayed using reverse-transcriptase polymerase chain reaction.Results: PC enhanced the mineralization of PDL cells in a dose-dependent manner in the OIM. Exogenous miR-31 and miR-146a expression upregulated alkaline phosphatase (ALP), bone morphogenic protein (BMP), and dentin matrix protein 1 (DMP1) expression. However, miR-31 and miR-146a modulates cementum protein 1 (CEMP1) expression in different ways. PC also enhanced ALP and BMP but attenuated CEMP1 in the OIM. Although the OIM or PC treatment upregulated miR-21, miR-29b, and miR-146a, only miR-146a was able to be induced by PC in combination with OIM.Conclusion: This study demonstrated that PC enhances the differentiation of PDL cells, especially osteogenic through miR-146a upregulation. In order to control the ankylosis after regenerative endodontics with the usage of bioaggregates, further investigations to explore these differentiation mechanisms in the miRNA level may be needed. [ABSTRACT FROM AUTHOR]

• The effect of temperature on the dynamic viscoelastic behavior of PDL was characterized. • At 37 °C, amounts of loss factor were found to be greater than those in 25 °C. • The viscous phase of the PDL in higher temperatures plays a critical role. Periodontal ligament (PDL) attaches tooth root to the surrounding bone. Its existence between tooth and jaw bone is of utmost importance due to its significant role in absorbing and distributing physiological and para-physiological loading. According to the previous studies, various mechanical tests have been performed to characterize the mechanical properties of the PDL; however, all of them have been done at room temperature. To the best of our knowledge, this is the first study in which the testing was performed at body temperature. The present research was planned to measure the dependency of PDL's viscoelastic behavior on temperature and frequency. Three different temperatures, including body and room temperature, were opted to perform the dynamic compressive tests of the bovine PDL. In addition, a Generalized Maxwell model (GMM) was presented based on empirical outcomes. At 37 °C, amounts of loss factor were found to be greater than those in 25 °C, which demonstrates that the viscous phase of the PDL in higher temperatures plays a critical role. Likewise, by raising the temperature from 25 °C to 37 °C, the model parameters show an enlargement in the viscous part and lessening in the elastic part. It was concluded that the PDL's viscosity in body temperature is much higher than that in room temperature. This model would be functional for a more accurate computational analysis of the PDL at the body temperature (37 °C) in various loading conditions such as orthodontic simulations, mastication, and impact. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein 2 (BMP-2) has a critical function in bone and cartilage development and in repairing damaged organs and tissue. However, clinical use of BMP-2 at doses of 0.5-1 mg/ml for orthopedics has been associated with severe postoperative swelling requiring emergency surgical intervention. We determined whether a high concentration of BMP-2 induces inflammatory responses in macrophages and the suppression of osteogenesis in hMSCs. We obtained human periodontal ligament stem cells and bone marrow stem cells from the maxilla, i.e., human mesenchymal stem cells (hMSCs), from the periodontal ligament of extracted third molar teeth and from the bone marrow of the maxilla, respectively. Osteogenic differentiation was measured by alkaline phosphatase activity and alizarin red S staining. Proteins were assessed by flow cytometry, enzyme-linked immunosorbent assay, Western blot and immunocytochemistry. Changes of gene expression were measured by reverse transcription plus the polymerase chain reaction (RT-PCR) and real-time PCR. A high BMP-2 concentration inhibited the early stages of osteogenesis in hMSCs. Co-culturing THP-1 cells (human monocytic cells) with hMSCs reduced the late stages of osteogenesis compared with those seen in hMSCs alone. In addition, high-dose BMP-2 induced the expression of inflammatory cytokines in THP-1 cells and the expression of the anti-inflammatory cytokine tumor-necrosis-factor-α-inducible gene 6 protein (TSG-6) in hMSCs. Consistent with the anti-inflammatory effects of hMSCs when co-cultured with THP-1 cells, interleukin-1β expression was downregulated by TSG-6 treatment of THP-1 cells. Our findings suggest that a high BMP-2 concentration triggers inflammation that causes inflammatory cytokine release from THP-1 cells, leading to the suppression of osteogenesis, whereas TSG-6 secreted by hMSCs suppresses inflammatory reactions through p38 and ERK in the mitogen-activated protein kinase pathway. [ABSTRACT FROM AUTHOR]

The ribosomal S6 kinase RSK2 is essential for osteoblast function, and inactivating mutations of RSK2 cause osteopenia in humans with Coffin-Lowry syndrome (CLS). Alveolar bone loss and premature tooth exfoliation are also consistently reported symptoms in CLS patients; however, the pathophysiologic mechanisms are unclear. Therefore, aiming to identify the functional relevance of Rsk2 for tooth development, we analyzed Rsk2-deficient mice. Here, we show that Rsk2 is a critical regulator of cementoblast function. Immunohistochemistry, histology, micro-computed tomography imaging, quantitative backscattered electron imaging, and in vitro assays revealed that Rsk2 is activated in cementoblasts and is necessary for proper acellular cementum formation. Cementum hypoplasia that is observed in Rsk2-deficient mice causes detachment and disorganization of the periodontal ligament and was associated with significant alveolar bone loss with age. Moreover, Rsk2-deficient mice display hypomineralization of cellular cementum with accumulation of nonmineralized cementoid. In agreement, treatment of the cementoblast cell line OCCM-30 with a Rsk inhibitor reduces formation of mineralization nodules and decreases the expression of cementum markers. Western blot analyses based on antibodies against Rsk1, Rsk2, and an activated form of the 2 kinases confirmed that Rsk2 is expressed and activated in differentiating OCCM-30 cells. To discriminate between periodontal bone loss and systemic bone loss, we additionally crossed Rsk2-deficient mice with transgenic mice overexpressing the osteoanabolic transcription factor Fra1. Fra1 overexpression clearly increases systemic bone volume in Rsk2-deficient mice but does not protect from alveolar bone loss. Our results indicate that cell autonomous cementum defects are causing early tooth loss in CLS patients. Moreover, we identify Rsk2 as a nonredundant regulator of cementum homeostasis, alveolar bone maintenance, and periodontal health, with all these features being independent of Rsk2 function in systemic bone formation. [ABSTRACT FROM AUTHOR]

Although many reports have been published on the functional roles of periodontal ligament (PDL) cells, the mechanisms involved in the maintenance and homeostasis of PDL have not been determined. We investigated the effects of biomechanical force on growth factor production, phosphorylation of MAPKs, and intracellular transduction pathways for growth factor production in human periodontal ligament (hPDL) cells using MAPK inhibitors. hPDL cells were exposed to mechanical force (6 MPa) using a hydrostatic pressure apparatus. The levels of growth factor mRNA and protein were examined by real-time RT-PCR and ELISA. The phosphorylation of MAPKs was measured using BD™ CBA Flex Set. In addition, MAPKs inhibitors were used to identify specific signal transduction pathways. Application of biomechanical force (equivalent to occlusal force) increased the synthesis of VEGF-A, FGF-2, and NGF. The application of biomechanical force increased the expression levels of phosphorylated ERK and p38, but not of JNK. Furthermore, the levels of VEGF-A and NGF expression were suppressed by ERK or p38 inhibitor. The growth factors induced by biomechanical force may play a role in the mechanisms of homeostasis of PDL. [ABSTRACT FROM AUTHOR]

Periodontal ligament-associated protein 1 (PLAP-1)/asporin is an extracellular matrix protein preferentially expressed in periodontal ligaments. PLAP-1/asporin inhibits the cytodifferentiation and mineralization of periodontal ligament cells and has important roles in the maintenance of periodontal tissue homeostasis. However, the involvement of PLAP-1/asporin in inflammatory responses during periodontitis is poorly understood. This study hypothesized that PLAP-1/asporin might affect the pathogenesis of periodontitis by regulating periodontopathic bacteria-induced inflammatory responses. Proinflammatory cytokine expression induced by Toll-like receptor 2 (TLR2) and TLR4 was significantly downregulated when PLAP-1/asporin was overexpressed in periodontal ligament cells. Similarly, recombinant PLAP-1/asporin inhibited TLR2- and TLR4-induced proinflammatory cytokine expression in macrophages. We also confirmed that NF-κB activity induced by TLR2 and TLR4 signaling was suppressed by the addition of recombinant PLAP-1/asporin. Furthermore, IκB kinase α degradation induced by TLR4 was reduced by PLAP-1/asporin. Immunoprecipitation assays demonstrated the binding abilities of PLAP-1/asporin to both TLR2 and TLR4. Taken together, PLAP-1/asporin negatively regulates TLR2- and TLR4-induced inflammatory responses through direct molecular interactions. These findings indicate that PLAP-1/asporin has a defensive role in periodontitis lesions by suppressing pathophysiologic TLR signaling and that the modulating effects of PLAP-1/asporin might be useful for periodontal treatments. [ABSTRACT FROM AUTHOR]

The exact mechanism by which focal adhesion kinase (FAK) translates mechanical signals into osteogenesis differentiation in force-subjected cells has not been elucidated. The responses to different forces differ according to the origin of cells and the type of stress applied. Therefore, the recruitment of osteoclast and osteoblast progenitor cells, and the balanced activation of these cells around and within the periodontal ligament (PDL) are essential for alveolar bone remodeling. Cells within the PDL and MG63 cells were subjected to tensile forces of −100 kPa for different periods of time. At various times during the tensile force application, they were processed for the purpose of analyzing cell viability, cell cycle, and osteogenic protein. The effect of small interfering RNA transfection targeting FAK was also evaluated. Tensile force enhanced a rapid increase in the phosphorylation of FAK and up-regulated osteogenic protein expression in PDL cells, but not in MG63 cells. Transfecting PDL cells with FAK antisense oligonucleotide diminished alkaline phosphatase and osteocalcin secretion. These findings suggest that tensile force activates FAK pathways in PDL cells, which down-regulate immune cytokine and up-regulate osteogenic protein. [ABSTRACT FROM AUTHOR]

Abstract: Cell surface integrin receptors mediate cell adhesion, migration and cellular signaling in all nucleated cells. They are activated by binding to extracellular ligands or by intracellular proteins, such as kindlins that engage with their cytoplasmic tails. Cells in the periodontal tissues express several integrins with overlapping ligand-binding capabilities. A distinct phenotype in the periodontium has only been described for knockouts or mutations of three integrin subunits, α11, β6 and β2. Integrin α11β1 appears to have some regulatory function in the periodontal ligament of continuously erupting incisors in mice. Integrin αvβ6 is expressed in the junctional epithelium (JE) of the gingiva. Animals deficient in this receptor develop classical signs of periodontal disease, including inflammation, apical migration of the JE and bone loss, suggesting that it plays a role in the regulation of periodontal inflmmation, likely through activation of transforming growth factor-β1. Lack of integrin activation in the JE is also associated with periodontitis. Patients with kindlin-1 mutations have severe early-onset periodontal disease. Finally, patients with mutations in the leukocyte-specific β2 integrin subunit have severe periodontal problems due to lack of transiting neutrophils in the periodontal tissues. [Copyright &y& Elsevier]