Lepr‐Expressing PDLSCs Contribute to Periodontal Homeostasis and Respond to Mechanical Force by Piezo1

Advanced Science, Journal Year: 2023, Volume and Issue: 10(29)

Published: Aug. 8, 2023

Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as distinct ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs located the peri-vascular niche, possessing multilineage potential contributing repair response injury. Ablation of disrupts Hyper-loading unloading occlusal forces modulate activation. Piezo1 is demonstrated that mediates mechanosensing conditional Piezo1-deficient mice. Meanwhile, Yoda1, selective activator Piezo1, significantly accelerates growth via induction cells. summary, Lepr marks unique multipotent PDLSC vivo, toward homeostasis Piezo1-mediated mechanosensing.

Language: Английский

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Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(3), P. 1899 - 1964

Published: Jan. 19, 2023

The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance which is crucial for orofacial homeostasis further linked to systemic health human psychosocial well-being. However, with limited ability self-repair, can often be impaired by traumatic, inflammatory, progressive insults, leading high prevalence tooth loss defects worldwide. Regenerative medicine holds promise achieve physiological restoration lost or damaged organs, in particular an evolving framework developmental engineering has pioneered functional regeneration harnessing odontogenic program. As a key event morphogenesis, mesenchymal condensation dictates dental tissue formation patterning through cellular self-organization signaling interaction epithelium, provides representative decipher organogenetic mechanisms leveraged regenerative purposes. In this review, we summarize how spatiotemporally assembles from stem cells (DSCs) sequentially mediates development. We highlight condensation-mimetic efforts based on ex vivo aggregation DSCs, have achieved functionally robust physiologically relevant after implantation animals humans. discussion aspect will add knowledge development-inspired strategies offer benefits propel clinical organ regeneration.

Language: Английский

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Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 14, 2024

Periodontitis affects billions of people worldwide. To address relationships periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas human periodontium (34-sample, 105918-cell), including sulcular junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states were enriched for effector cytokines periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence situ hybridization detected intracellular 16 S mRNA signals multiple correlated SK/JK proinflammatory phenotypes situ. Cell-cell communication analysis predicted keratinocyte-specific innate adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) peri-epithelial foci, cells often spatially constrained around JKs. Spatial phenotyping immunosuppressed JK-microniches SK-localized tertiary lymphoid structures Here, demonstrate impacts on interactomics SK JK health which requires further investigation to support precision interventions chronic inflammation.

Language: Английский

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Periodontal tissue stem cells and mesenchymal stem cells in the periodontal ligament

Japanese Dental Science Review, Journal Year: 2022, Volume and Issue: 58, P. 172 - 178

Published: May 17, 2022

Periodontal tissue stem cells, which play a crucial role in maintaining the homeostasis of periodontal tissues, are found ligament (PDL). These cells have long been referred to as mesenchymal stem/stromal (MSCs), and their clinical applications extensively studied. However, PDL not thoroughly investigated, they may be different from MSCs. Recent advances cell biology, such genetic lineage tracing, identification label-retaining single-cell transcriptome analysis, made it possible analyze vivo. In this review, we summarize recent findings on these populations discuss future research directions toward developing regenerative therapy.

Language: Английский

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A Roadmap for the Human Oral and Craniofacial Cell Atlas

Journal of Dental Research, Journal Year: 2022, Volume and Issue: 101(11), P. 1274 - 1288

Published: Sept. 26, 2022

Oral and craniofacial tissues are uniquely adapted for continuous intricate functioning, including breathing, feeding, communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, variously composed of epithelia, vessels, cartilage, bone, teeth, ligaments, muscles, as well mesenchymal, adipose, peripheral nervous tissue. Recent single cell spatial multiomics assays—specifically, genomics, epigenomics, transcriptomics, proteomics, metabolomics—have annotated known new types states in human animal models, but concepts remain limitedly explored the postnatal oral complex. Here, we highlight collaborative coordinated efforts newly established Craniofacial Bionetwork part Human Cell Atlas, which aims to leverage approaches first understand cellular molecular makeup health then address common rare diseases. These powerful assays have already revealed that support tissues, they will unravel networks utilized across development, maintenance, aging those affected diseases This level integration annotation with partner laboratories globe be critical understanding how multiple variables, such age, sex, race, ancestry, influence niches. 1) recent employ resolve our collective biology at a higher resolution disease, 2) discuss vision behind Bionetwork, 3) outline stakeholders who contribute benefit from network, 4) directions creating Atlas.

Language: Английский

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Application of scRNA-seq in Dental Research: Seeking Regenerative Clues From the Structure of Tooth and Periodontium in Physical or Pathological States

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 21, 2025

This review presents a comprehensive overview of single-cell RNA sequencing (scRNA-seq) analyses used to study tooth and periodontal tissues. The intricate cellular composition both teeth periodontium are revealed, leading the identification new cell types tracing lineage profiles for each type. Herein, we summarize progression dental tissue formation, homeostasis, regenerative mechanisms. scRNA-seq have demonstrated that constituent ratio tissues transforms homeostasis or injury repair. Importantly, data in diseased change intercellular communication patterns compared normal state. These findings provide valuable insights into underlying disease mechanisms at level context vision, thereby facilitating investigation potential therapeutic interventions.

Language: Английский

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Current Topics in Dental Follicle Cell Research

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 12, 2025

Dental follicle cells (DFCs) are dental stem that can only be obtained from tooth germs or after extraction of unerupted wisdom teeth. For many years, DFCs have been studied in basic research and preclinical studies regenerative dentistry, as they involved both the development periodontium eruption. Since first isolation, number with has increased. This article summarizes most important articles last five years to provide an overview current topics. The focus was on research. Basic includes eruption, well into molecular mechanisms during osteogenic differentiation. In addition, focused therapies immunotherapies also discussed. These new show improved our understanding periodontal regeneration. DFC is for dentistry future; however, indicate significant progress still needed before integrated routine clinical practice.

Language: Английский

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Compression force regulates cementoblast mineralization via S1PR1/mitophagy axis

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 4, 2025

Abstract Orthodontically induced inflammatory root resorption (OIIRR) poses a significant clinical challenge, as excessive orthodontic force shortens tooth longevity by impairing cementoblast‐mediated cementum mineralization and promoting resorption. Cementoblasts, essential for mineralized formation resistance to resorption, exhibit altered mechanosensitivity mechanotransduction under force, yet the role of mitophagy in this process remains poorly understood. In study, we investigated how S1PR1/mitophagy axis modulates cementoblast OIIRR progression. The vivo loading model revealed that heavy compression triggered impaired along with suppression cementoblasts downregulating PINK1 PARKIN expression. vitro experiments further confirmed increased reactive oxygen species (ROS) levels, disrupted mitochondrial membrane potential (MMP), inhibited OCCM30 cells, thereby their capacity. Mechanistically, S1PR1 upregulation activated mitophagy, which turn restored force. Moreover, pharmacological activation SEW2871 alleviated vivo. These findings highlight pivotal maintaining function offering novel insights into molecular mechanisms underlying suggesting therapeutic strategies prevent during treatment.

Language: Английский

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The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering

Bioactive Materials, Journal Year: 2025, Volume and Issue: 49, P. 418 - 436

Published: March 18, 2025

Language: Английский

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Diverse stem cells for periodontal tissue formation and regeneration

genesis, Journal Year: 2022, Volume and Issue: 60(8-9)

Published: Aug. 2, 2022

Summary The periodontium is comprised of multiple units mineralized and nonmineralized tissues including the cementum on root surface, alveolar bone, periodontal ligament (PDL), gingiva. PDL contains a variety cell populations mesenchymal stem/progenitor cells (MSCs) termed PDLSCs, which contribute to regeneration. Recent studies utilizing mouse genetic models shed light identities these progenitors in their native environment, particularly regarding how they homeostasis repair periodontium. current concept that are localized perivascular niche. Single‐cell RNA sequencing (scRNA‐seq) analyses reveal heterogeneity cell‐type specific markers periodontium, as well developmental relationship with precursor dental follicle. characteristics PDLSCs diversity vivo now beginning be unraveled thanks insights from scRNA‐seq analyses, aid uncover fundamental properties stem human PDL. new knowledge will highly important for developing more effective cell‐based regenerative therapies future.

Language: Английский

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