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Journal of Periodontal Research Apr 2019Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent... (Review)
Review
Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent stem/progenitor cells include the periodontal ligament stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the gingival mesenchymal stem/progenitor cells (G-MSCs), and the alveolar bone proper stem/progenitor cells (AB-MSCs). Whereas inflammation is regarded as the reason for tissue damage, it also remains a fundamental step of any early healing process. In performing their periodontal tissue regenerative/reparative activity, periodontal stem/progenitor cells interact with their surrounding inflammatory micro-environmental, through their expressed receptors, which could influence their fate and the outcome of any periodontal stem/progenitor cell-mediated reparative/regenerative activity. The present review discusses the current understanding about the interaction of periodontal stem/progenitor cells with their surrounding inflammatory micro-environment, elaborates on the inflammatory factors influencing their stemness, proliferation, migration/homing, differentiation, and immunomodulatory attributes, the possible underlying intracellular mechanisms, as well as their proposed relationship to the canonical and noncanonical Wnt pathways.
Topics: Alveolar Process; Cell Differentiation; Cell Movement; Cell Proliferation; Gingiva; Humans; Immunomodulation; Inflammation; Multipotent Stem Cells; Periodontal Ligament; Periodontium; Regeneration; Stem Cells; Tooth Apex; Wnt Signaling Pathway
PubMed: 30295324
DOI: 10.1111/jre.12616 -
Cells Mar 2022Periodontal disease can cause irreversible damage to tooth-supporting tissues such as the root cementum, periodontal ligament, and alveolar bone, eventually leading to... (Review)
Review
Periodontal disease can cause irreversible damage to tooth-supporting tissues such as the root cementum, periodontal ligament, and alveolar bone, eventually leading to tooth loss. While standard periodontal treatments are usually helpful in reducing disease progression, they cannot repair or replace lost periodontal tissue. Periodontal regeneration has been demonstrated to be beneficial in treating intraosseous and furcation defects to varied degrees. Cell-based treatment for periodontal regeneration will become more efficient and predictable as tissue engineering and progenitor cell biology advance, surpassing the limitations of present therapeutic techniques. Stem cells are undifferentiated cells with the ability to self-renew and differentiate into several cell types when stimulated. Mesenchymal stem cells (MSCs) have been tested for periodontal regeneration in vitro and in humans, with promising results. Human umbilical cord mesenchymal stem cells (UC-MSCs) possess a great regenerative and therapeutic potential. Their added benefits comprise ease of collection, endless source of stem cells, less immunorejection, and affordability. Further, their collection does not include the concerns associated with human embryonic stem cells. The purpose of this review is to address the most recent findings about periodontal regenerative mechanisms, different stem cells accessible for periodontal regeneration, and UC-MSCs and their involvement in periodontal regeneration.
Topics: Humans; Mesenchymal Stem Cells; Periodontal Ligament; Periodontium; Tissue Engineering; Umbilical Cord
PubMed: 35406732
DOI: 10.3390/cells11071168 -
Modern Rheumatology Nov 2018Tendons and ligaments play essential roles in connecting muscle and bone and stabilizing the connections between bones. The damage to tendons and ligaments caused by... (Review)
Review
Tendons and ligaments play essential roles in connecting muscle and bone and stabilizing the connections between bones. The damage to tendons and ligaments caused by aging, injury, and arthritis induces the dysfunction of the musculoskeletal system and reduces the quality of life. Current therapy for damaged tendons and ligaments depends on self-repair; however, it is difficult to reconstruct normal tissue. Regeneration therapy for tendons and ligaments has not been achieved, partly because the mechanism, cell biology, and pathophysiology of tendon and ligament development remain unclear. This review summarizes the role of the transcription factor, Mohawk, which controls tendon and ligament cell differentiation, in the maintenance of cell homeostasis, as well as its function in disease and the possibility of new therapeutic approaches.
Topics: Animals; Cell Differentiation; Homeodomain Proteins; Homeostasis; Humans; Intervertebral Disc; Periodontal Ligament; Tenocytes
PubMed: 29667905
DOI: 10.1080/14397595.2018.1466644 -
Archives of Oral Biology Mar 2015Periodontal ligament cells (PDLCs) respond to various mechanical stimuli, including mastication and orthodontic force, and thereby play an important functional role. A... (Review)
Review
Periodontal ligament cells (PDLCs) respond to various mechanical stimuli, including mastication and orthodontic force, and thereby play an important functional role. A number of in vitro models have been widely used to study these mechanoresponses. Here, we comprehensively review the various in vitro mechanical loading approaches used for assessing PDLCs, including their force generation properties, mechanical characteristics, and simulation of authentic bioprocesses. Furthermore, we highlight the evolution of current cytomechanical studies, from conventional two-dimensional to novel three-dimensional (3-D) cell cultures. Some representative 3-D PDLC culture and mechanical loading systems are also described, with the advantages and limitations of these discussed. From this review, we can conclude that optimal mechanical loading models must be chosen to match the specific research purpose, and that novel 3-D PDLC culture and mechanical loading models are promising for future studies.
Topics: Biomechanical Phenomena; Cell Culture Techniques; In Vitro Techniques; Periodontal Ligament; Pressure; Stress, Mechanical
PubMed: 25526626
DOI: 10.1016/j.archoralbio.2014.11.012 -
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 -
ACS Applied Materials & Interfaces Jun 2022The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth...
The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth (dental implants) provides a cost-effective solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After transplantation into the rat renal capsule, only the titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through bone sialoprotein expression and phosphorus metabolism, which are critical for cementogenesis. Therefore, the titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.
Topics: Animals; Biomimetics; Osseointegration; Periodontal Ligament; Periodontium; Rats; Titanium
PubMed: 35695310
DOI: 10.1021/acsami.2c06679 -
Journal of Periodontal Research Jan 2022The 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...
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.
Topics: Animals; Dental Cementum; Lipopolysaccharides; Maxilla; Periodontal Ligament; Rats; Rats, Sprague-Dawley
PubMed: 34839547
DOI: 10.1111/jre.12946 -
Microscopy (Oxford, England) Jan 2022Cell-to-cell communication orchestrates various cell and tissue functions. This communication enables cells to form cellular networks with each other through direct... (Review)
Review
Cell-to-cell communication orchestrates various cell and tissue functions. This communication enables cells to form cellular networks with each other through direct contact via intercellular junctions. Because these cellular networks are closely related to tissue and organ functions, elucidating the morphological characteristics of cellular networks could lead to the development of novel therapeutic approaches. The tooth, periodontal ligament (PDL) and alveolar bone form a complex via collagen fibres. Teeth depend on the co-ordinated activity of this complex to maintain their function, with cellular networks in each of its three components. Imaging methods for three-dimensional (3D) mesoscopic architectural analysis include focused ion beam/scanning electron microscopy (FIB/SEM), which is characterized by its ability to select observation points and acquire data from complex tissue after extensive block-face imaging, without the need to prepare numerous ultrathin sections. Previously, we employed FIB/SEM to analyse the 3D mesoscopic architecture of hard tissue including the PDL, which exists between the bone and tooth root. The imaging results showed that the cementum, PDL and alveolar bone networks are in contact and form a heterogeneous cellular network. This cellular network may orchestrate mechanical loading-induced remodelling of the cementum-PDL-alveolar bone complex as the remodelling of each complex component is coordinated, as exemplified by tooth movement due to orthodontic treatment and tooth dislocation due to occlusal loss. In this review, we summarize and discuss the 3D mesoscopic architecture of cellular networks in the cementum, PDL and alveolar bone as observed in our recent mesoscopic and morphological studies.
Topics: Bone and Bones; Dental Cementum; Periodontal Ligament
PubMed: 34850074
DOI: 10.1093/jmicro/dfab051 -
Journal of Clinical Periodontology Dec 2017Tumour necrosis factor (TNF)-α is a pathological factor causing the characteristic symptoms of periodontal disease and rheumatoid arthritis. In this study, we describe...
AIM
Tumour necrosis factor (TNF)-α is a pathological factor causing the characteristic symptoms of periodontal disease and rheumatoid arthritis. In this study, we describe the phenotypes of human TNF-α transgenic mice (hTNFtg) with respect to their periodontium and the temporomandibular joint (TMJ).
MATERIAL AND METHODS
Periodontal structures, TMJ and skull shape of hTNFtg mice and wild-type (WT) littermates were assessed by microcomputed tomography, automated segmentation, geometric morphometrics and histologic ground sections.
RESULTS
We show that hTNFtg mice have an eroded lamina dura and reduced periodontal ligament space compared to (WT) littermates. Transgenic mice further exhibit severe destruction of the TMJ. Geometric morphometrics revealed that hTNFtg mice have a more laterally positioned TMJ with a concomitantly enlarged zygomatic process. Mandibular and maxillary teeth occluded properly.
CONCLUSIONS
Our findings suggest that chronic inflammation in hTNFtg mice causes destructive changes of the periodontium and the TMJ.
Topics: Animals; Arthritis, Rheumatoid; Bone Resorption; Humans; Inflammation; Mice; Mice, Transgenic; Osteoclasts; Periodontal Ligament; Periodontium; Phenotype; Skull; Temporomandibular Joint; Tumor Necrosis Factor-alpha; X-Ray Microtomography; Zygoma
PubMed: 28833486
DOI: 10.1111/jcpe.12799 -
Periodontal ligament stem cells in the periodontitis niche: inseparable interactions and mechanisms.Journal of Leukocyte Biology Sep 2021Periodontitis is characterized by the periodontium's pathologic destruction due to the host's overwhelmed inflammation to the dental plaque. The bacterial infections and... (Review)
Review
Periodontitis is characterized by the periodontium's pathologic destruction due to the host's overwhelmed inflammation to the dental plaque. The bacterial infections and subsequent host immune responses have shaped a distinct microenvironment, which generally affects resident periodontal ligament stem cells (PDLSCs). Interestingly, recent studies have revealed that impaired PDLSCs may also contribute to the disturbance of periodontal homeostasis. The putative vicious circle underlying the interesting "positive feedback" of PDLSCs in the periodontitis niche remains a hot research topic, whereas the inseparable interactions between resident PDLSCs and the periodontitis niche are still not fully understood. This review provides a microscopic view on the periodontitis progression, especially the quick but delicate immune responses to oral dysbacterial infections. We also summarize the interesting crosstalk of the resident PDLSCs with their surrounding periodontitis niche and potential mechanisms. Particularly, the microenvironment reduces the osteogenic properties of resident PDLSCs, which are closely related to their reparative activity. Reciprocally, these impaired PDLSCs may disrupt the microenvironment by aggravating the host immune responses, promoting aberrant angiogenesis, and facilitating the osteoclastic activity. We further recommend that more in-depth studies are required to elucidate the interactions of PDLSCs with the periodontal microenvironment and provide novel interventions for periodontitis.
Topics: Cell Communication; Humans; Immunity; Models, Biological; Periodontal Ligament; Periodontitis; Stem Cells
PubMed: 34043832
DOI: 10.1002/JLB.4MR0421-750R