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Journal of Dental Research Sep 2022Bone sialoprotein (gene: ; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a...
Bone sialoprotein (gene: ; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a key regulator of mineralized tissue formation via evolutionarily conserved functional domains, including a C-terminal integrin-binding Arg-Gly-Asp (RGD) domain implicated in extracellular matrix-cell signaling. Ablation of in mice () results in impaired bone growth and mineralization and defective osteoclastogenesis, with effects in the craniofacial region including reduced acellular cementum formation, detachment of the periodontal ligament (PDL), alveolar bone hypomineralization, and severe periodontal breakdown. We hypothesized that BSP-RGD plays an important role in cementum and alveolar bone formation and mineralization, as well as periodontal function. This hypothesis was tested by replacing the RGD motif with a nonfunctional Lys-Ala-Glu (KAE) sequence in () mice and OCCM.30 murine () cementoblasts. The RGD domain was not critical for acellular or cellular cementum formation in mice. However, PDL volume and thickness were increased, and significantly more tartrate-resistant acid phosphatase-positive osteoclasts were found on alveolar bone surfaces of mice versus wild type mice. PDL organization was disrupted as indicated by picrosirius red stain, second harmonic generation imaging, dynamic mechanical analysis, and decreased asporin proteoglycan localization. In vitro studies implicated RGD functions in cell migration, adhesion, and mineralization, and this was confirmed by an ossicle implant model where cells lacking BSP-RGD showed substantial defects as compared with controls. In total, the BSP-RGD domain is implicated in periodontal development, though the scale and scope of changes indicated by in vitro studies indicate that other factors may partially compensate for and reduce the phenotypic severity of mice lacking BSP-RGD in vivo.
Topics: Animals; Dental Cementum; Integrin-Binding Sialoprotein; Mice; Oligopeptides; Periodontal Ligament
PubMed: 35686360
DOI: 10.1177/00220345221100794 -
BioMed Research International 2022, . To investigate the effect of ginsenoside Rg1 on the biological activity of primary cultured human periodontal ligament cells (PDLC). . The effects of ginsenoside Rg1...
, . To investigate the effect of ginsenoside Rg1 on the biological activity of primary cultured human periodontal ligament cells (PDLC). . The effects of ginsenoside Rg1 on the proliferation activity, protein synthesis, and alkaline phosphatase (ALP) activity of primary cultured human periodontal ligament cells were investigated by thiazole blue (MTT) colorimetric method, Coomassie brilliant blue method, and enzyme kinetics method. The effect of ginsenoside Rg1 on cell cycle was detected by flow cytometry, and the cells were labeled with calcium ion-sensitive fluorescent probe Fluo3/AM, and the effect of ginsenoside Rg1 on intracellular free calcium concentration was detected by laser scanning confocal microscope. . Compared with the control group, the experimental groups of ginsenoside Rg1 at various concentrations could significantly promote cell proliferation, and the effect time was the longest in the concentration range of 0.01-0.05 mol/L;, Rg1 0.01umol/L and 0.05umol/L. The protein content in the 72-hour cell culture medium of the mol/L group was significantly higher than that of the control group; the ALP activity in the 72-hour cell culture medium of the Rg1 0.01 mol/L, 0.05 mol/L, and 0.1 mol/L groups was significantly higher than that of the control group; FCM assay showed that after 0.1 mol/L Rg1 for 48 hours, compared with the control group, the proportion of cells in the early stage of DNA synthesis (G1%) of PDLC was significantly reduced, while the proportion of cells in the DNA synthesis stage (S%) and the value of cell proliferation index PrI (S + G2M)% were significantly increased; Rg1 increased intracellular calcium in PDLC cells at first and then decreased and finally maintained at a slightly higher resting calcium level than before drug addition. . Ginsenoside Rg1 can increase the proliferation activity, protein synthesis, and alkaline phosphatase activity of periodontal ligament cells within a certain concentration range; Rg1 reduces the cells in G1 phase and increases cells in S phase of periodontal ligament fibroblasts. Change the concentration of free calcium ions in cells and promote more cells to enter a proliferative state.
Topics: Alkaline Phosphatase; Calcium; Cells, Cultured; Ginsenosides; Humans; Periodontal Ligament
PubMed: 35813231
DOI: 10.1155/2022/7576359 -
Biomolecules Mar 2022Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and... (Review)
Review
Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues' architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.
Topics: Cell Differentiation; Periodontal Ligament; Technology; Tissue Engineering; Tissue Scaffolds
PubMed: 35327627
DOI: 10.3390/biom12030435 -
Biochimica Et Biophysica Acta.... May 2018Jaw discrepancies and malrelations affect a large proportion of the general population and their treatment is of utmost significance for individuals' health and quality... (Review)
Review
Jaw discrepancies and malrelations affect a large proportion of the general population and their treatment is of utmost significance for individuals' health and quality of life. The aim of their therapy is the modification of aberrant jaw development mainly by targeting the growth potential of the mandibular condyle through its cartilage, and the architectural shape of alveolar bone through a suture type of structure, the periodontal ligament. This targeted treatment is achieved via external mechanical force application by using a wide variety of intraoral and extraoral appliances. Condylar cartilage and sutures exhibit a remarkable plasticity due to the mechano-responsiveness of the chondrocytes and the multipotent mesenchymal cells of the sutures. The tissues respond biologically and adapt to mechanical force application by a variety of signaling pathways and a final interplay between the proliferative activity and the differentiation status of the cells involved. These targeted therapeutic functional alterations within temporo-mandibular joint ultimately result in the enhancement or restriction of mandibular growth, while within the periodontal ligament lead to bone remodeling and change of its architectural structure. Depending on the form of the malrelation presented, the above treatment approaches, in conjunction or separately, lead to the total correction of jaw discrepancies and the achievement of facial harmony and function. Overall, the treatment of craniofacial and jaw anomalies can be seen as an interplay of mechanical forces and adaptations occurring within temporo-mandibular joint and alveolar bone. The aim of the present review is to present up-to-date knowledge on the mechano-biology behind jaw growth modification and alveolar bone remodeling. Furthermore, future molecular targeted therapeutic strategies are discussed aiming at the improvement of mechanically-driven chondrogenesis and osteogenesis.
Topics: Animals; Bone Remodeling; Cell Proliferation; Humans; Mandible; Mandibular Diseases; Periodontal Ligament; Stress, Mechanical; Temporomandibular Joint
PubMed: 29454076
DOI: 10.1016/j.bbadis.2018.02.007 -
Journal of Nanobiotechnology Jul 2023Although various new biomaterials have enriched the methods for periodontal regeneration, their efficacy is still controversial, and the regeneration of damaged support...
Nanosilicate-functionalized nanofibrous membrane facilitated periodontal regeneration potential by harnessing periodontal ligament cell-mediated osteogenesis and immunomodulation.
Although various new biomaterials have enriched the methods for periodontal regeneration, their efficacy is still controversial, and the regeneration of damaged support tissue in the periodontium remains challenging. Laponite (LAP) nanosilicate is a layered two-dimensional nanoscale, ultrathin nanomaterial with a unique structure and brilliant biocompatibility and bioactivity. This study aimed to investigate the effects of nanosilicate-incorporated PCL (PCL/LAP) nanofibrous membranes on periodontal ligament cells (PDLCs) in vitro and periodontal regeneration in vivo. A PCL/LAP nanofibrous membrane was fabricated by an electrospinning method. The characterization of PCL/LAP nanofibrous membrane were determined by scanning electron microscopy (SEM), energy dispersive spectrum of X-ray (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and tensile test. The proliferation and osteogenic differentiation of PDLCs on the PCL/LAP nanofibrous membrane were evaluated. A PDLCs and macrophage coculture system was used to explore the immunomodulatory effects of the PCL/LAP nanofibrous membrane. PCL/LAP nanofibrous membrane was implanted into rat calvarial and periodontal defects, and the regenerative potential was evaluated by microcomputed topography (micro-CT) and histological analysis. The PCL/LAP nanofibrous membrane showed good biocompatibility and bioactivity. It enhanced the proliferation and osteogenic differentiation of PDLCs. The PCL/LAP nanofibrous membrane also stimulated anti-inflammatory and pro-remodeling N2 neutrophil formation, regulated inflammatory responses and induced M2 macrophage polarization by orchestrating the immunomodulatory effects of PDLCs. The PCL/LAP nanofibrous membrane promoted rat calvarial defect repair and periodontal regeneration in vivo. LAP nanosilicate-incorporated PCL membrane is capable of mediating osteogenesis and immunomodulation of PDLCs in vitro and accelerating periodontal regeneration in vivo. It could be a promising biomaterial for periodontal regeneration therapy.
Topics: Rats; Animals; Periodontal Ligament; Osteogenesis; Nanofibers; Biocompatible Materials; Cell Differentiation; Immunomodulation; Regeneration; Tissue Scaffolds
PubMed: 37443072
DOI: 10.1186/s12951-023-01982-4 -
Cells Jan 2024Orthodontic tooth movement (OTM) is thought to be impeded by bisphosphonate (BP) therapy, mainly due to increased osteoclast apoptosis and changes in the periodontal...
Orthodontic tooth movement (OTM) is thought to be impeded by bisphosphonate (BP) therapy, mainly due to increased osteoclast apoptosis and changes in the periodontal ligament (PdL), a connecting tissue between the alveolar bone and teeth. PdL cells, mainly fibroblasts (PdLFs), are crucial regulators in OTM by modulating force-induced local inflammatory processes. Recently, we identified the TGF-β/BMP superfamily member GDF15 as an important modulator in OTM, promoting the pro-inflammatory mechanoresponses of PdLFs. The precise impact of the highly potent BP zoledronate (ZOL) on the mechanofunctionality of PdLFs is still under-investigated. Therefore, the aim of this study was to further characterize the ZOL-induced changes in the initial inflammatory mechanoresponse of human PdLFs (hPdLFs) and to further clarify a potential interrelationship with GDF15 signaling. Thus, two-day in vitro treatment with 0.5 µM, 5 µM and 50 µM of ZOL altered the cellular properties of hPdLFs partially in a concentration-dependent manner. In particular, exposure to ZOL decreased their metabolic activity, the proliferation rate, detected using Ki-67 immunofluorescent staining, and survival, analyzed using trypan blue. An increasing occurrence of DNA strand breaks was observed using TUNEL and an activated DNA damage response was demonstrated using H2A.X (phosphoS139) staining. While the osteogenic differentiation of hPdLFs was unaffected by ZOL, increased cellular senescence was observed using enhanced p21 and β-galactosidase staining. In addition, cytokine-encoding genes such as , , and , which are associated with a senescence-associated secretory phenotype, were up-regulated by ZOL. Subsequently, this change in the hPdLF phenotype promoted a hyperinflammatory response to applied compressive forces with an increased expression of the pro-inflammatory markers , and , as well as the activation of monocytic THP1 cells. GDF15 appeared to be particularly relevant to these changes, as siRNA-mediated down-regulation balanced these hyperinflammatory responses by reducing IL-1β and IL-6 expression (IL1B -value < 0.0001; IL6 -value < 0.001) and secretion (IL-1β -value < 0.05; IL-6 -value < 0.001), as well as immune cell activation (-value < 0.0001). In addition, ZOL-related reduced RANKL/OPG values and inhibited osteoclast activation were enhanced in -deficient hPdLFs (both -values < 0.0001; all statistical tests: one-way ANOVA, Tukey's post hoc test). Thus, GDF15 may become a promising new target in the personalized orthodontic treatment of bisphosphonatepatients.
Topics: Humans; Fibroblasts; Growth Differentiation Factor 15; Interleukin-6; Osteogenesis; Periodontal Ligament; Zoledronic Acid
PubMed: 38247838
DOI: 10.3390/cells13020147 -
International Journal of Environmental... Feb 2023Herein Finite elements analysis (FEA) study assesses the adequacy and accuracy of five failure criteria (Von Mises (VM), Tresca, maximum principal (S1), minimum...
Herein Finite elements analysis (FEA) study assesses the adequacy and accuracy of five failure criteria (Von Mises (VM), Tresca, maximum principal (S1), minimum principal (S3), and Hydrostatic pressure) for the study of tooth as a structure (made of enamel, dentin, and cement), along with its stress absorption-dissipation ability. Eighty-one 3D models of the second lower premolar (with intact and 1-8 mm reduced periodontium) were subjected to five orthodontic forces (intrusion, extrusion, tipping, rotation, and translation) of 0.5 N (approx. 50 gf) (in a total of 405 FEA simulations). Only the Tresca and VM criteria showed biomechanically correct stress display during the 0-8 mm periodontal breakdown simulation, while the other three showed various unusual biomechanical stress display. All five failure criteria displayed comparable quantitative stress results (with Tresca and VM producing the highest of all), showing the rotational and translational movements to produce the highest amount of stress, while intrusion and extrusion, the lowest. The tooth structure absorbed and dissipated most of the stress produced by the orthodontic loads (from a total of 0.5 N/50 gf only 0.125 N/12.5 gf reached PDL and 0.01 N/1 gf the pulp and NVB). The Tresca criterion seems to be more accurate than Von Mises for the study of tooth as structure.
Topics: Tooth Movement Techniques; Stress, Mechanical; Periodontal Ligament; Periodontium; Finite Element Analysis; Computer Simulation; Models, Biological
PubMed: 36901151
DOI: 10.3390/ijerph20054133 -
European Cells & Materials Jan 2023Periodontitis is a progressive disease that ultimately leads to bone and tooth loss. A major consequence of periodontal disease is the inability to regain lost bone in...
Periodontitis is a progressive disease that ultimately leads to bone and tooth loss. A major consequence of periodontal disease is the inability to regain lost bone in the periodontium. The importance was demonstrated of glucose-regulated protein-78 (GRP78) in the osteogenic differentiation of periodontal ligament stem cells and their potential use for regeneration of the periodontium. Previous studies have shown the relationship between GRP78 and dentine matrix protein-1 (DMP1). The importance of this receptor-ligand complex in supporting the process of osteogenesis and angiogenesis was confirmed in this study. To show the function of GRP78 in mineralised tissues, transgenic periodontal ligament stem cells (PDLSCs) were generated in which GRP78 was either overexpressed or silenced. Gene expression analysis of the cells cultured under osteogenic conditions showed an increase in key osteogenic genes with the overexpression of GRP78. RNA-Seq analysis was also performed to understand the transcriptome profile associated with genotype changes. Using the database for annotation, visualisation, and integration discovery (DAVID) for the functional enrichment analysis of differentially expressed genes, the upregulation of genes promoting osteogenesis and angiogenesis with GRP78 overexpression was demonstrated. Alizarin red staining and scanning electron microscopy analysis revealed matrix mineralisation with increased calcium deposition in GRP78 overexpressing cells. The in vivo osteogenic and angiogenic function of GRP78 was shown using a subcutaneous implantation rodent model. The results suggested that GRP78 in PDLSCs can regulate the expression of both osteogenesis and angiogenesis. Therefore, GRP78 could be considered as a therapeutic target for repair of diseased periodontium.
Topics: Cell Differentiation; Cells, Cultured; Endoplasmic Reticulum Chaperone BiP; Osteogenesis; Periodontal Ligament; Stem Cells; Neovascularization, Physiologic
PubMed: 36683528
DOI: 10.22203/eCM.v045a02 -
Progress in Orthodontics Nov 2023To investigate the displacement of dentition and stress distribution on periodontal ligament (PDL) during retraction and intrusion of anterior teeth under different...
The displacement of teeth and stress distribution on periodontal ligament under different upper incisors proclination with clear aligner in cases of extraction: a finite element study.
OBJECTIVES
To investigate the displacement of dentition and stress distribution on periodontal ligament (PDL) during retraction and intrusion of anterior teeth under different proclination of incisors using clear aligner (CA) in cases involving extraction of the first premolars.
METHODS
Models were constructed, consisting of the maxilla, PDLs, CA and maxillary dentition without first premolars. These models were then imported to finite element analysis (FEA) software. The incisor proclination determined the division of the models into three groups: Small torque (ST) with U1-SN = 100°, Middle torque (MT) with U1-SN = 110°, and High torque (HT) with U1-SN = 120°. Following space closure, a 200 g intrusion force was applied at angles of 60°, 70°, 80°, and 90° to the occlusal plane, respectively.
RESULTS
CA therapy caused lingual tipping and extrusion of incisors, mesial tipping and intrusion of canines, and mesial tipping of posterior teeth in each group. As the proclination of incisors increased, the incisors presented more extrusion and minor retraction, and the teeth from the canine to the second molar displayed an increased tendency of intrusion. The peak Von Mises equivalent stress (VMES) value successively decreased from the central incisor to the canine and from the second premolar to the second molar, and the VMES of the second molar was the lowest among the three groups. When the angle between the intrusion force and occlusal plane got larger, the incisors exhibited greater intrusion but minor retraction.
CONCLUSIONS
The "roller coaster effect" usually occurred in cases involving premolar extraction with CA, especially in patients with protruded incisors. The force closer to the vertical direction were more effective in achieving incisor intrusion. The stress on PDLs mainly concentrated on the cervix and apex of incisors during the retraction process, indicating a possibility of root resorption.
Topics: Female; Humans; Periodontal Ligament; Incisor; Finite Element Analysis; Molar; Orthodontic Appliances, Removable
PubMed: 37981597
DOI: 10.1186/s40510-023-00491-2 -
Advanced Science (Weinheim,... May 2024The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose...
The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell-extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL-matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross-linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster-relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin-focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell-ECM interactions. In vivo experiments confirm that faster-relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration.
Topics: Periodontal Ligament; Regeneration; Hydrogels; Biocompatible Materials; Animals; Stress, Mechanical; Humans; Cells, Cultured; Viscosity; Poloxamer; Stem Cells; Elasticity; Cell Differentiation
PubMed: 38460171
DOI: 10.1002/advs.202309562