Biomedical subjects

P M Bartold

Publications and source records attributed to P M Bartold.

At least 19 recordsLinked to original sources

PubMed2006

Ovine periodontal ligament stem cells: isolation, characterization, and differentiation potential.

Periodontal disease leads to destruction of the connective tissues responsible for restraining teeth within the jaw. To date, various conventional therapies for periodontal regeneration have shown limited and variable clinical outcomes. Recent studies have suggested that newly identified human periodontal ligament stem cells (PDLSCs) may offer an alternate and more reliable strategy for the treatment of periodontal disease using a cell-based tissue engineering approach. In the present study, we generated enriched preparations of PDLSCs derived from ovine periodontal ligament using immunomagnetic bead selection, based on expression of the mesenchymal stem cell-associated antigen CD106 (vascular cell adhesion molecule 1). These CD106+ ovine PDLSCs demonstrated the capacity to form adherent clonogenic clusters of fibroblast-like cells when plated at low densities in vitro. Ex vivo-expanded ovine PDLSCs exhibited a high proliferation rate in vitro and expressed a phenotype (CD44+, CD166+, CBFA-1+, collagen-I+, bone sialoprotein+) consistent with human-derived PDLSCs. Furthermore, cultured ovine PDLSCs expressed high transcript levels of the ligament/tendon-specific early transcription factor scleraxis. Importantly, ex vivo-expanded ovine PDLSCs demonstrated the capacity to regenerate both cementum-like mineral and periodontal ligament when transplanted into NOD/SCID mice. The results from the present study suggest that ovine PDLSCs may potentially be used as a novel cellular therapy to facilitate successful and more predictable regeneration of periodontal tissue using an ovine preclinical model of periodontal disease as a prelude to human clinical studies.

Adult Stem Cells↗

PubMed2006

The epithelial cell rests of Malassez--a role in periodontal regeneration?

This article reviews general aspects about the epithelial cell rests of Malassez (ERM). The historical and general morphological features of the ERM are briefly described. The embryological derivation of the ERM is presented as an important consideration in understanding the events associated with their origin and possible functional roles within the periodontal ligament. The ultrastructural description of the ERM is also included to complement the morphological characteristics which distinguish these cells as the unique epithelial element of the periodontal ligament. The unique ability of these cells to synthesize and secrete a number of proteins usually associated with cells of mesenchymal origin, rather than ectodermal origin, is discussed in light of their role in cementum repair and regeneration. Such considerations lead to our hypothesis that one of the functional roles of the ERM may lie not only their role in maintaining and contributing to the normal periodontal cellular elements and function but also contributing, in a significant manner, to periodontal regeneration.

Animals↗

PubMed2006

Location of putative stem cells in human periodontal ligament.

BACKGROUND AND OBJECTIVE: The origin of cells in the mature periodontium, and the location of their progenitors, are still unknown. It is also unknown whether inflammation influences the number and distribution of these cells within the periodontium. Molecules such as STRO-1, CD146 and CD44 have been identified on a variety of mesenchymal stem cells. The aim of this study was to identify and localize putative stem cells in diseased and healthy human periodontal ligament using cell-surface markers for mesenchymal stem cells. MATERIAL AND METHODS: Healthy and periodontitis-affected teeth were collected, fixed in 10% neutral-buffered formalin, decalcified and embedded in paraffin in preparation for immunohistochemistry. Antibodies against STRO-1, CD146 and CD44 were used to identify putative stem cells in the periodontal ligament. RESULTS: Putative stem cells were identified in both healthy and diseased periodontal ligament. They were mainly located in the paravascular region and small clusters of cells were also found in the extravascular region. Wider distributions of these cells were detected in sections of diseased ligament. CONCLUSION: Within the periodontal ligament of both healthy and diseased teeth, cells have been identified consistent with their identification as putative stem cells. The presence of an inflammatory reaction associated with periodontitis may enhance the number of these cells.

Animals↗

PubMed2006

Stem cells in the periodontal ligament.

The ability to identify and manipulate stem cells has been a significant advancement in regenerative medicine and has contributed to the development of tissue engineering-based clinical therapies. Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques such as tissue engineering need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. One of the critical requirements for a tissue engineering approach is the delivery of ex vivo expanded progenitor populations or the mobilization of endogenous progenitor cells capable of proliferating and differentiating into the required tissues. By definition, stem cells fulfill these requirements and the recent identification of stem cells within the periodontal ligament represents a significant development in the progress toward predictable periodontal regeneration. In order to explore the importance of stem cells in periodontal wound healing and regeneration, this review will examine contemporary concepts in stem cell biology, the role of periodontal ligament progenitor cells in the regenerative process, recent developments in identifying periodontal stem cells and the clinical implications of these findings.

Animals↗

PubMed2006

Dentinal hypersensitivity: a review.

Tooth sensitivity is a very common clinical presentation which can cause considerable concern for patients. This condition is frequently encountered by periodontists, dentists, hygienists and dental therapists. The management of this condition requires a good understanding of the complexity of the problem, as well as the variety of treatments available. This review considers the aetiology, incidence and management of dentinal hypersensitivity.

Dentin Sensitivity↗

PubMed2005

Enhanced proliferation, attachment and osteopontin expression by porcine periodontal cells exposed to Emdogain.

Emdogain (EMD) is an enamel matrix derivative extracted from developing porcine teeth with demonstrated periodontal regenerative potential. EMD has been shown to influence a number of properties of periodontal ligament cells including proliferation, cell attachment and matrix synthesis. To date, the effect of EMD on the epithelial cell rests of Malassez (ERM) is unknown. In this study, periodontal ligament fibroblasts, ERM, alveolar bone cells and gingival fibroblasts were obtained from porcine periodontal ligament, alveolar bone and gingiva. This study investigated, in vitro, the effect of EMD at three concentrations on proliferation, cell attachment and expression of mRNA for two mineralised tissue-related proteins (osteopontin and bone sialoprotein). As for other periodontal cells, the ERM proliferative response was enhanced by EMD. Attachment assays revealed a highly significant increase for ERM and gingival fibroblasts after EMD treatment at all concentrations. This study has also shown that EMD stimulated expression of osteopontin mRNA by ERM and alveolar bone cells. The results from this study provide evidence that EMD enhanced cellular events related with proliferation, attachment and osteopontin mRNA expression by porcine periodontal cells, in a manner consistent with its role in periodontal regenerative therapy.

Animals↗

PubMed2005

Use of the Vector scaling unit in supportive periodontal therapy: a subjective patient evaluation.

BACKGROUND: Patient discomfort is one reason for poor compliance with supportive periodontal therapy (SPT). The aim of this study was to compare the levels of discomfort during SPT, using the Vector system and treatment with a conventional ultrasonic scaler. METHODS: Forty-six patients with an SPT programme were debrided using both the Vector system and a conventional piezo-electric scaler (Sirona) in a split mouth design. A visual analogue scale was used to evaluate of pain scores upon completion of treatment. A verbal response scale(VRS) was used to assess discomfort, vibration and noise associated with the scaling system, as well as the volume and taste of the coolant used by these systems. RESULTS: Patients instrumented with the Vector system experienced approximately half the amount of pain compared with the conventional ultrasonic scaling system. The VRS showed that the Vector system caused less discomfort than the conventional ultrasonic scaling system when assessed for pain, vibration, noise and volume of coolant. These findings were all statistically significant. There was, however, no statistically significant difference between the two systems when assessed for taste. CONCLUSION: During SPT the Vector system caused reduced discomforting sensations compared with conventional methods and may be useful in improving compliance with SPT programmes.

Adult↗

PubMed2005

The efficacy of mesenchymal stem cells to regenerate and repair dental structures.

OBJECTIVES: Identification, characterization, and potential application of mesenchymal stem cells (MSC) derived from human dental tissues. METHODS: Dental pulp and periodontal ligament were obtained from normal human impacted third molars. The tissues were digested in collagenase/dispase to generate single cell suspensions. Cells were cultured in alpha-MEM supplemented with 20% fetal bovine serum, 2 mM l-glutamine, 100 microM l-ascorbate-2-phosphate. Magnetic and fluorescence activated cell sorting were employed to characterize the phenotype of freshly isolated and ex vivo expanded cell populations. The developmental potential of cultured cells was assessed following co-transplantation with hydroxyapetite/tricalcium phosphate (HA/TCP) particles into immunocompromised mice for 8 weeks. RESULTS: MSC were identified in adult human dental pulp (dental pulp stem cells, DPSC), human primary teeth (stem cells from human exfoliated deciduous teeth, SHED), and periodontal ligament (periodontal ligament stem cells, PDLSC) by their capacity to generate clongenic cell clusters in culture. Ex vivo expanded DPSC, SHED, and PDLSC populations expressed a heterogeneous assortment of makers associated with MSC, dentin, bone, smooth muscle, neural tissue, and endothelium. PDLSC were also found to express the tendon specific marker, Scleraxis. Xenogeneic transplants containing HA/TCP with either DPSC or SHED generated donor-derived dentin-pulp-like tissues with distinct odontoblast layers lining the mineralized dentin-matrix. In parallel studies, PDLSC generated cementum-like structures associated with PDL-like connective tissue when transplanted with HA/TCP into immunocompromised mice. CONCLUSION: Collectively, these data revealed the presence of distinct MSC populations associated with dental structures with the potential of stem cells to regenerate living human dental tissues in vivo.

Animals↗

PubMed2005

Periodontitis and rheumatoid arthritis: a review.

Periodontitis and rheumatoid arthritis (RA) appear to share many pathologic features. In this review, the common pathologic mechanisms of these two common chronic conditions are explored. Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and RA. While this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to experience more significant periodontal problems compared to their non-RA counterparts, and vice versa. A case is made that these two diseases could be very closely related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of such dysfunction is still unknown. Nonetheless, there is accruing evidence to support the notion that both conditions manifest as a result of an imbalance between proinflammatory and anti-inflammatory cytokines. As a result, new treatment strategies are expected to emerge for both diseases that may target the inhibition of proinflammatory cytokines and destructive proteases. The clinical implications of the current data dictate that patients with RA should be carefully screened for their periodontal status.

Animals↗

PubMed2004

Immunohistochemical localization and expression of fibromodulin in adult rat periodontium and inflamed human gingiva.

OBJECTIVE: The aim of this study was to determine the distribution and expression of fibromodulin in adult rat periodontal tissues and inflamed human gingiva. MATERIALS AND METHODS: The distribution of fibromodulin in rat molar periodontium and human gingival tissue was studied by immunohistochemistry. The expression of fibromodulin mRNA from human gingival fibroblasts, periodontal ligament fibroblasts and osteoblasts was studied by reverse transcription-polymerase chain reaction (RT-PCR). For comparative purposes, the distribution and mRNA expression of collagen types I and III, as well as the two small leucine-rich proteoglycans decorin and biglycan were also studied. RESULTS: In the adult rat periodontium, fibromodulin was distributed in the suprabasal gingival epithelium, gingival and periodontal fibroblasts as well as their surrounding extracellular matrices. Strong expression was noted in the palatal gingival tissues and the interfaces of the periodontal ligament with alveolar bone and cementum. In human gingival tissues, staining of fibromodulin was detected in the connective tissue of inflamed gingiva associated with both gingivitis and periodontitis; whereas, weak staining for this molecule was noted in healthy gingival tissues. The expression of mRNA for fibromodulin was strongest in the cultured osteoblasts. Periodontal ligament fibroblasts showed only a weak level of expression for fibromodulin mRNA. CONCLUSIONS: Fibromodulin is differentially expressed throughout the periodontium being primarily associated with collagen type I in non-mineralized sites. In addition fibromodulin showed an upregulation in inflamed gingival tissue.

Animals↗

PubMed2004

Prevalence of systemic diseases in Brisbane general and periodontal practice patients.

BACKGROUND: Periodontitis has been associated with a number of systemic diseases such as atherosclerosis, coronary heart diseases, and respiratory diseases. This study aimed to determine whether there is a significant difference in the prevalence of systemic diseases (a) in patients referred for periodontal care compared to the general practice population, (b) in patients attending a public hospital and private practices, (c) in patients attending public and private periodontal practices, and (d) among patients with periodontitis of varying severity. METHODS: Charts of 1000 adult patients were selected from four clinics (University of Queensland (UQ) School of Dentistry Admissions Clinic, UQ School of Dentistry Periodontics Clinic, Private Periodontal Practice, and Private General Dental Practice). The prevalence of medical conditions was evaluated using validated self-reported health questionnaires. The periodontal condition was assessed from the most recent relevant radiographs in the files. RESULTS: Periodontal patients had a higher prevalence of systemic diseases compared to the general practice population. Public patients had a greater prevalence of systemic diseases compared to patients in private practice for both general practice and periodontal patients. In patients with advanced periodontitis, bronchitis, hepatitis and rheumatoid arthritis were most prevalent. Patients with periodontitis also took more medications and were more likely to suffer from multiple conditions compared to the general dental population. CONCLUSIONS: Patients attending public dental facilities have an increased prevalence of systemic disease compared to those attending private practices. Furthermore periodontal patients have a greater prevalence of diseases compared to general practice patients. Patients with moderate or advanced periodontitis show an increase in the prevalence of some systemic diseases previously reported to be risk factors for periodontal disease.

Adult↗

PubMed2004

Modulating effect of serum on the stimulation of plasminogen activator inhibitor 2 production in human gingival fibroblasts by lipopolysaccharide and interleukin-1beta.

OBJECTIVE: Plasminogen activator inhibitor-2 (PAI-2) is an important counter proteolysis factor which helps protect tissues from inflammatory stress. The expression of PAI-2 can be modulated by various inflammatory stimulants and mediators. The aim of the present study was to investigate how serum factors, might modulate the effects of lipopolysaccharide (LPS) and interleukin-1beta on PAI-2 production by human gingival fibroblasts. METHODS: Human gingival fibroblasts were exposed to LPS derived from Actinobacillus actinomycetemcomitans or Escherichia coli and a commercial source of interleukin-1beta (IL-1beta). The expression of PAI-2 and its mRNA was monitored by Western blotting, RT-PCR, and Northern blotting. RESULTS: The results showed that the distribution of PAI-2 synthesised by human gingival fibroblasts (HGF) was mostly as an intracellular protein (47kDa). The presence of serum in the culture media was absolutely necessary for both the secretion of PAI-2 and for the effect of the inflammatory mediators (LPS and IL-1beta). A pattern of PAI-2 response in HGF after LPS stimulation was detected with a quick up-regulation of the PAI-2 mRNA, which was down regulated when extracellular PAI-2 (60kDa mass) levels reached plateau levels. The synthesis of PAI-2 by HGF, in terms of mRNA expression and protein synthesis, was more sensitive to stimulation with lower concentrations of LPS (10 ng/ml) than with higher LPS concentrations. CONCLUSIONS: PAI-2 is a serum dependent molecule with major cytosolic localisation in HGF. Its cellular accumulation and secretion can be modulated by bacterial LPS and IL-1beta through serum factors.

Analysis of Variance↗

PubMed2003

[Immunohistochemical localization and expression of fibromodulin in the periodontium].

OBJECTIVE: To study the distribution and expression of fibromodulin in normal periodontium, so as to understand its role in periodontal tissue homeostasis. METHODS: Five normal male Lewis rats were killed and their bilateral mandibular first molars with surrounding alveolar bones and gingival tissues were taken out. Human gingival fibroblasts, fibroblasts of periodontal ligament, and osteoblasts were cultured. Immunohistochemistry with anti-fibromodulin, anti-decorin, anti-biglycan, anti-type I collagen, and anti-type III collagen antibodies and RT-PCR were used to detect the tissue distribution and cellular localization of fibromodulin and related proteoglycans, decorin and biglycan, and type I and type III collagens. RESULTS: Fibromodulin was strongly expressed in the suprabasal gingival epithelium, periodontal ligament, alveolar bone, gingival and periodontal fibroblasts as well as their matrices. Strong expression was noted in the area close to oral gingival aspect and the interfaces of periodontal ligament-alveolar bone and periodontal-ligament-cementum. Decorin was strongly expressed in the area close to the gingival sulcus in gingival tissue. Biglycan was stained evidently in gingival epithelium. Fibromodulin, decorin and biglycan mRNAs were strongly expressed in osteoblasts. mRNAs of type I and type III collagens were strongly expressed in gingival fibroblasts. CONCLUSION: Fibromodulin may interact with other small proteoglycans to regulate the network formation of periodontal collagen fibers, and may be involved in mineralization of the alveolar bone and cementum.

Animals↗

PubMed2003

Immunohistochemical localisation of extracellular matrix proteins in the periodontium during cementogenesis in the rat molar.

OBJECTIVE: The development of the periodontium involves the coordinated expression of numerous extracellular matrix (ECM) macromolecules and their receptors (integrins). The aim of this study was to determine the expression of selected hard and soft tissue matrix molecules and the integrin alpha5beta1 in the periodontal tissues, during cementogenesis in the rat molar. METHODS: Using immunohistochemical methods, the distribution of the extracellular matrix proteins, fibronectin, tenascin, and bone sialoprotein (BSP), as well as the integrin subunits alpha5 and beta1 were studied in rats aged 3, 5 and 8 weeks. RESULTS: Fibronectin was widely distributed in the gingival epithelium, gingival connective tissue and in the periodontal ligament. Tenascin expression was less marked compared with fibronectin, but was more distinctly associated with cells and peri-cellular areas of the epithelial-connective tissue interface, the gingiva and within the periodontal ligament. The fibronectin-receptor alpha5beta1 integrins were expressed by epithelial cells, periodontal ligament cells and gingival fibroblasts. A notable finding was the increased staining intensity of fibronectin, tenascin and alpha5beta1 integrin in all 5-week old molar sections in the periodontal ligament matrix and cells, apical to the cemento-enamel junction (CEJ) along the alveolar crest (AC) ridge height. Bone sialoprotein was distinctly associated with the hard tissues of the periodontium as acellular cementum and alveolar bone matrix expressed bone sialoprotein throughout all sections, in all age groups. CONCLUSIONS: In conclusion, this study has demonstrated the selective distribution of several hard and soft tissue matrix molecules during periodontogenesis. The results highlight the complex nature of interactions of various proteins and molecules during development. The interactions between these molecules and their specific roles in development and regeneration await further investigation.

Animals↗

PubMed2003

Inter-relationships between rheumatoid arthritis and periodontal disease. A review.

This review considers the considerable similarities between periodontal disease and rheumatoid arthritis (RA). While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are remarkably similar and it is possible that individuals manifesting both periodontitis and RA may suffer from a unifying underlying systemic dysregulation of the inflammatory response. In light of these findings, the implications for the use of disease-modifying medications in the management of these two chronic inflammatory conditions is apparent. Further longitudinal studies and medication-based intervention studies are required to determine just how closely these two conditions are allied.

Arthritis, Rheumatoid↗

PubMed2003

Effect of Emdogain on human periodontal fibroblasts in an in vitro wound-healing model.

OBJECTIVE: The aim of this study was to evaluate the influence of Emdogain (EMD) on cultured gingival fibroblasts, periodontal ligament fibroblasts and dermal fibroblasts, using an in vitro model of wound healing. BACKGROUND: Enamel matrix derivative has been demonstrated to promote periodontal regeneration. However, the precise mechanisms by which this agent acts are still unclear. METHODS: The effect of EMD on proliferation of the cells was studied using subconfluent cultures of gingival fibroblasts and periodontal ligament fibroblasts. The cells were made quiescent overnight and then stimulated with various concentrations of EMD (10, 50, 100 and 150 microg/ml) for 24 h. Negative and positive controls were cells cultured in media containing 0.2% and 10% fetal calf serum (FCS). The DNA synthesis was measured by the cellular uptake of [3H]thymidine. For in vitro wounding the cells were cultured, wounded and stimulated with 0.2% FCS, 10% FCS and EMD at a concentration of 20 microg/ml. The percentage of wound fill after treatment was measured after d 1, 4, 6, 12 and 16. The proliferation of cells was also calculated by the extent of incorporation of crystal violet. RESULTS: The results demonstrated that cells in vitro fill an empty space by a combination of proliferation and cell migration. The most rapid closure of a wound area occurred where both proliferation and migration can occur as was seen when wounded cultures were maintained in 10% FCS or at a concentration of 20 microg/ml EMD which promoted proliferation. CONCLUSIONS: Therefore, EMD appears to exert an influence on cells that is compatible with improved wound healing.

Analysis of Variance↗

PubMed2003

Growth hormone regulates osteogenic marker mRNA expression in human periodontal fibroblasts and alveolar bone-derived cells.

BACKGROUND: Growth hormone (GH) is a potent regulator of bone formation. The proposed mechanism of GH action is through the stimulation of osteogenic precursor cell proliferation and, following clonal expansion of these cells, promotion of differentiation along the osteogenic lineage. OBJECTIVES: We tested this hypothesis by studying the effects of GH on primary cell populations of human periodontal ligament cells (PLC) and alveolar bone cells (ABC), which contain a spectrum of osteogenic precursors. METHODS: The cell populations were assessed for mineralization potential after long-term culture in media containing beta-glycerophosphate and ascorbic acid, by the demonstration of mineral deposition by Von Kossa staining. The proliferative response of the cells to GH was determined over a 48-h period using a crystal violet dye-binding assay. The profile of the cells in terms of osteogenic marker expression was established using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for alkaline phosphatase (ALP), osteopontin, osteocalcin, bone sialoprotein (BSP), as well as the bone morphogenetic proteins BMP-2, BMP-4 and BMP-7. RESULTS: As expected, a variety of responses were observed ranging from no mineralization in the PLC populations to dense mineralized deposition observed in one GH-treated ABC population. Over a 48-h period GH was found to be non-mitogenic for all cell populations. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) BSP mRNA expression correlated well with mineralizing potential of the cells. The change in the mRNA expression of the osteogenic markers was determined following GH treatment of the cells over a 48-h period. GH caused an increase in ALP in most cell populations, and also in BMP expression in some cell populations. However a decrease in BSP, osteocalcin and osteopontin expression in the more highly differentiated cell populations was observed in response to GH. CONCLUSION: The response of the cells indicates that while long-term treatment with GH may promote mineralization, short-term treatment does not promote proliferation of osteoblast precursors nor induce expression of late osteogenic markers.

Alkaline Phosphatase↗

PubMed2003

Immunohistochemical localization of fibromodulin in the periodontium during cementogenesis and root formation in the rat molar.

BACKGROUND: Cementum is essential for periodontal regeneration, as it provides anchorage between the root surface and the periodontal ligament. A variety of macromolecules present in the extracellular matrix of the periodontium, including proteoglycans, are likely to play a regulatory role in cementogenesis. Recently, the small leucine-rich proteoglycan, fibromodulin, has been isolated from bovine periodontal ligament and localized in bovine cementum, as well as in human periodontal ligament. OBJECTIVE: The aim of this study was to examine the distribution of fibromodulin during cementogenesis and root formation. METHODS: A standard indirect immunoperoxidase technique was employed, using an antifibromodulin polyclonal antibody on sections of molar teeth from rats aged 3, 5 and 8 weeks. RESULTS: Immunoreactivity to fibromodulin was evident in the periodontal ligament in all sections. An intense positive stain was observed in the extracellular matrix where the periodontal ligament fibers insert into the alveolar bone and where the Sharpey's fibers insert into the cementum. There was no staining evident in the mineralized cellular and acellular cementum. The intensity of immunoreactivity to the antifibromodulin antibody increased proportionally with increasing tissue maturation. CONCLUSION: The results from this study suggest that fibromodulin is a significant component of the extracellular matrix in the periodontal ligament during development, and may play a regulatory role in the mineralization process or maintaining homeostasis at the hard-soft tissue interface during cementogenesis.

Animals↗