-
Journal of Dental Research Oct 2023The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within...
The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.
Topics: Animals; Epithelial Attachment; Gingiva; Mastication; Connective Tissue; Biology; Epithelium
PubMed: 37555395
DOI: 10.1177/00220345231185288 -
International Journal of Oral Science Oct 2023X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization...
X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Topics: Mice; Male; Female; Animals; Familial Hypophosphatemic Rickets; Bone and Bones; Tooth; Periodontal Ligament
PubMed: 37813865
DOI: 10.1038/s41368-023-00252-1 -
Journal of Nanobiotechnology Jan 2024Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth... (Review)
Review
Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.
Topics: Humans; Periodontitis; Periodontium; Anti-Bacterial Agents; Regeneration; Immunomodulation; Immunity
PubMed: 38178140
DOI: 10.1186/s12951-023-02261-y -
Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis.Nature Communications Jun 2024Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated...
Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.
Topics: Humans; Keratinocytes; Single-Cell Analysis; Periodontitis; Cell Communication; Cytokines; Periodontium; Immunity, Innate; In Situ Hybridization, Fluorescence; Male; Metagenomics; Bacteria; Female; Adult; Adaptive Immunity
PubMed: 38876998
DOI: 10.1038/s41467-024-49037-y -
Current Stem Cell Research & Therapy 2024Periodontium is an important tooth-supporting tissue composed of both hard (alveolar bone and cementum) and soft (gingival and periodontal ligament) sections. Due to the... (Review)
Review
BACKGROUND AND OBJECTIVES
Periodontium is an important tooth-supporting tissue composed of both hard (alveolar bone and cementum) and soft (gingival and periodontal ligament) sections. Due to the multi-tissue architecture of periodontium, reconstruction of each part can be influenced by others. This review focuses on the bone section of the periodontium and presents the materials used in tissue engineering scaffolds for its reconstruction.
MATERIALS AND METHODS
The following databases (2015 to 2021) were electronically searched: ProQuest, EMBASE, SciFinder, MRS Online Proceedings Library, Medline, and Compendex. The search was limited to English-language publications and studies.
RESULTS
Eighty-three articles were found in primary searching. After applying the inclusion criteria, seventeen articles were incorporated into this study.
CONCLUSION
In complex periodontal defects, various types of scaffolds, including multilayered ones, have been used for the functional reconstruction of different parts of periodontium. While there are some multilayered scaffolds designed to regenerate alveolar bone/periodontal ligament/cementum tissues of periodontium in a hierarchically organized construct, no scaffold could so far consider all four tissues involved in a complete periodontal defect. The progress and material considerations in the regeneration of the bony part of periodontium are presented in this work to help investigators develop tissue engineering scaffolds suitable for complete periodontal regeneration.
Topics: Humans; Periodontal Ligament; Periodontium; Tooth; Tissue Engineering; Tissue Scaffolds; Bone Regeneration
PubMed: 36578254
DOI: 10.2174/1574888X18666221227142055 -
European Journal of Orthodontics Jul 2023Orthodontic tooth movement (OTM) has previously been considered an inflammatory process. However, recent studies suggest that exosomes may play an important role in the...
BACKGROUND
Orthodontic tooth movement (OTM) has previously been considered an inflammatory process. However, recent studies suggest that exosomes may play an important role in the cellular microenvironment of OTM. microRNAs (miRNAs) are one of the major constituents of exosomes. This study aims to investigate the biological characteristics of miRNAs secreted by exosomes of periodontal ligament stem cells (PDLSCs) due to mechanical forces.
MATERIALS AND METHODS
First, we established a mechanical stress model. The PDLSCs were loaded under different force values and exosomes were extracted after 48 h. High-throughput sequencing of exosomal miRNAs was performed to further evaluate their biological functions and underlying mechanisms.
RESULTS
The morphology and functions of exosomes were not significantly different between the loading and non-loading PDLSC groups. The optimal loading time and force were 48 h and 1 g/cm2, respectively. After sequencing, gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) pathway and network analyses were performed and 10 differentially expressed miRNAs were identified according to a literature search. These are miR-99a-5p, miR-485-3P, miR-29a-3p,miR-21-5p, miR-146a-5p, miR140-3p, miR-1306-5p, miR-126-5p, miR-125a-5p, and miR-23a-3p.
LIMITATIONS
Extracting exosomes needs a large amount of PDLSCs. More functional experiments need to be done to confirm the exact mechanism of exosomal miRNAs of PDLSCs due to mechanical force.
CONCLUSIONS
The expression levels of miRNAs secreted by PDLSC-derived exosomes due to mechanical force were very different compared to PDLSC-derived exosomes under nonmechanical stress. The function of many of the identified exosomal miRNAs was found to be related to osteoblasts and osteoclasts. Further validation is required. A functional investigation of these miRNA could provide novel insights into their mechanism.
Topics: Humans; MicroRNAs; Exosomes; Periodontal Ligament; Stem Cells
PubMed: 37262013
DOI: 10.1093/ejo/cjad002 -
Journal of Periodontal Research Oct 2023To verify the role of YAP/WNT5A/FZD4 axis in stretch-induced osteogenic differentiation of hPDLCs.
OBJECTIVE
To verify the role of YAP/WNT5A/FZD4 axis in stretch-induced osteogenic differentiation of hPDLCs.
BACKGROUND
During orthodontic tooth movement, differentiation of human periodontal ligament cells (hPDLCs) at the tension side of the periodontal ligament mediates new bone formation. WNT5A promotes osteogenesis and its regulator Yes-associated protein (YAP) is responsive to mechanical stimulation in hPDLCs. However, the mechanisms of YAP and WNT5A in alveolar bone remodeling remain unclear.
METHODS
Cyclic stretch was applied to hPDLCs to mimic the orthodontic stretching force. Osteogenic differentiation was determined by alkaline phosphatase (ALP) activity, Alizarin Red staining, qRT-PCR and western blotting. To detect activation of YAP and expression of WNT5A and its receptor Frizzled-4 (FZD4), western blotting, immunofluorescence, qRT-PCR and ELISA were performed. Verteporfin, Lats-IN-1, small interfering RNAs and recombinant protein were used to explore the relationship of YAP, WNT5A and FZD4, and the effect of their relationship on stretch-induced osteogenesis of hPDLCs.
RESULTS
WNT5A, FZD4 and nuclear localization of YAP were upregulated by cyclic stretch. YAP positively regulated WNT5A and FZD4 expression and osteogenic differentiation of hPDLCs under cyclic stretch by YAP inhibition or activation assay. Knockdown of WNT5A and FZD4 attenuated YAP-induced and stretch-induced osteogenic differentiation. Recombinant WNT5A rescued the suppressed osteogenic differentiation by YAP inhibitor in hPDLCs, whereas knockdown of FZD4 weakened the effect of WNT5A and amplified the suppression.
CONCLUSIONS
WNT5A/FZD4 could be positively regulated by YAP and the YAP/WNT5A/FZD4 axis mediated osteogenic differentiation of hPDLCs under cyclic stretch. This study provided further insight into the biological mechanism of orthodontic tooth movement.
Topics: Humans; Osteogenesis; Periodontal Ligament; Cells, Cultured; Cell Differentiation; Proteins; Wnt-5a Protein; Frizzled Receptors
PubMed: 37340863
DOI: 10.1111/jre.13143 -
Journal of Clinical Periodontology Apr 2024To investigate the mechanisms by which periodontal ligament cells (PDLCs) convert biomechanical stimulation into inflammatory microenvironment inducing root resorption...
AIM
To investigate the mechanisms by which periodontal ligament cells (PDLCs) convert biomechanical stimulation into inflammatory microenvironment inducing root resorption (RR).
MATERIALS AND METHODS
RNA sequencing was employed to explore mechanisms in force-inflammatory signal transduction. Then resorption volume, odontoclastic activity, PDLC pyroptotic ratio and NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis pathway activation were analysed under force and pyroptosis inhibition. Further osteoclast formation, macrophage number and transwell polarization demonstrated the effects of PDLC pyroptosis on osteoclastogenesis and M1 polarization.
RESULTS
RNA sequencing revealed that NLRP3-mediated PDLC pyroptosis induced by Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)/NLRP3 pathway may be involved in mechano-inflammatory signal transduction. PDLC pyroptosis under force and the expression of NLRP3-mediated pyroptosis pathway in force-enhanced PDLCs were significantly increased, both in vivo and in vitro. MCC950 administration was sufficient to reduce PDLC pyroptosis and alleviate RR, odontoclast formation and M1 polarization in vivo. Further in vitro exploration showed that MCC950 treatment reduced PDLC force-promoted pyroptosis and blocked NLRP3-mediated pyroptosis pathway. Moreover, by treating THP-1 with force-pretreated PDLCs or supernatants, NLRP3-mediated PDLC pyroptotic released products induced osteoclast formation and M1 polarization.
CONCLUSIONS
NLRP3-mediated PDLC pyroptosis promotes RR. PDLCs transmit excessive force into inflammation signals through TLR4/NFκB/NLRP3 pathway, inducing PDLC pyroptosis, which directly promotes odontoclast formation and subsequent RR or promotes M1 polarization to indirectly trigger odontoclastogenesis and RR.
Topics: Humans; NLR Proteins; NLR Family, Pyrin Domain-Containing 3 Protein; Toll-Like Receptor 4; Periodontal Ligament; Pyroptosis; Root Resorption
PubMed: 38164052
DOI: 10.1111/jcpe.13914 -
Inflammation Oct 2023As a chronic inflammatory disease, periodontitis involves many biological processes including autophagy. At the same time, casein kinase 2 interacting protein-1 (CKIP-1)...
As a chronic inflammatory disease, periodontitis involves many biological processes including autophagy. At the same time, casein kinase 2 interacting protein-1 (CKIP-1) was reported to play a role in regulation of inflammation. But whether CKIP-1 and autophagy interact in periodontitis remains unclear. In this paper, our research team verified the levels of CKIP-1 expression and autophagy increase in the periodontal tissues of a ligature-induced periodontitis mouse model. And this result was also confirmed in Porphyromonas gingivalis (Pg)-induced human gingival fibroblasts (HGF) and human periodontal ligament cells (PDLC). We also showed the autophagy level in periodontal tissues is higher in Ckip-1 knockout (KO) mice than wild type (WT). At the same time, CKIP-1 knockdown lentivirus was used in PDLC and HGF, and it was found that silencing CKIP-1 significantly activated autophagy. Unfortunately, the regulatory role of autophagy in periodontitis is still unclear. Then, the autophagy agonist Rapamycin and inhibitor 3-MA were used in a periodontitis mouse model to investigate periodontal tissue destruction. We found the inflammation in periodontal tissue was reduced when autophagy activated. All these conclusions have been verified both in vivo and in vitro experiments. Finally, our research proved that silencing CKIP-1 reduces the expression of inflammatory cytokines in Pg-induced PDLC and HGF by regulating autophagy. Overall, a new role for CKIP-1 in regulating periodontal tissue inflammation was demonstrated in our study, and it is possible to treat periodontitis by targeting the CKIP-1 gene.
Topics: Mice; Animals; Humans; Inflammation; Periodontitis; Gingiva; Cytokines; Porphyromonas gingivalis; Autophagy; Carrier Proteins
PubMed: 37351817
DOI: 10.1007/s10753-023-01856-9 -
Journal of Materials Science. Materials... Nov 2023The aim of this study is to systematically appraise the evidence on available full thickness 3D gingival and mucosal models (3D culture in scaffold base system) and... (Review)
Review
The aim of this study is to systematically appraise the evidence on available full thickness 3D gingival and mucosal models (3D culture in scaffold base system) and their application in periodontal and peri-implant research. This study involved a systematic review of twenty-two studies obtained from searching from five electronic databases: MEDLINE-OVID, EMBASE, EBSCOhost, Web of Science Core Collection and LILACS, as well as a hand search of eligible articles up to September 2022. A total of 2338 studies were initially identified, after removal of duplicates (573), abstracts/title selection (1765), and full text screening (95), twenty-two studies were included, thirty-seven models were identified. Several cellular markers were reported by the studies included. The expression of keratinocytes differentiation markers (K4, K5, K10, K13, K14, K16, K17, K18, K19, involucrin, laminin5), proliferation marker (Ki67, CD90), and vimentin, Type I, II and IV collagen produced by fibroblasts were investigated in thirty models. No quantitative analyses were performed, and results of the review confirmed a substantial level of heterogeneity across experiments. In conclusion, there is currently insufficient evidence to conclude that the available 3D gingival and mucosal models can entirely recapitulate the human gingival tissue/mucosa and provide a useful research tool for periodontal and peri-implant research. This review also highlighted the lack of a standardized protocol to construct and characterize 3D gingival models. A new protocol is proposed for the characterization of in vitro gingival models for future research.
Topics: Humans; Gingiva; Evidence Gaps; Fibroblasts; Keratinocytes
PubMed: 37938480
DOI: 10.1007/s10856-023-06761-z