Francisco H Nociti

National Institutes of Health, Maryland, United States

Are you Francisco H Nociti?

Claim your profile

Publications (175)406.64 Total impact

  • Francisco H. Nociti, Marcio Z. Casati, Poliana Mendes Duarte
    [Show abstract] [Hide abstract]
    ABSTRACT: This literature review provides an overview of the current scenario regarding the impact of smoking on the progression and treatment of periodontitis; clinical, microbiological and immunological data from studies from our and other groups are presented. In general, preclinical and clinical data are unanimous in demonstrating that smokers present increased susceptibility, greater severity and faster progression of periodontal disease compared with nonsmokers. The evidence further demonstrates that smokers lose more teeth and have a less favorable response to therapy than do nonsmokers. Although it is well established that smoking significantly impacts on the onset, progression and outcome of periodontal disease, the mechanisms involved remain unclear. More importantly, some of the reported deleterious effects of smoking on periodontal tissues have been reported to be reversible upon participation in smoking-cessation programs. Therefore, clinicians should strongly advise smokers to enroll in cessation strategies, even temporarily, in order to improve the overall outcome.
    Periodontology 2000 02/2015; 67(1). · 4.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate (Pi) to mineral inhibitor pyrophosphate (PPi), where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.International Journal of Oral Science advance online publication, 12 December 2014; doi:10.1038/ijos.2014.62.
    International Journal of Oral Science 12/2014; · 2.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A full understanding of the key regulators controlling periodontal development and homeostasis is necessary for the design of improved periodontal regenerative therapies. Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules suggested to regulate collagen organization and cell signaling. Mice with double-deficiency of 2 SLRPs, fibromodulin and biglycan (dKO), acquire skeletal abnormalities, but their roles in regulating the periodontium remain undefined and were the focus of our studies. Transmission electron microscopy studies showed abnormal collagen fibrils in the periodontal ligament (PDL) and altered remodeling of alveolar bone in dKO mice. Immunohistochemistry (IHC) revealed increased staining of SLRPs (asporin, lumican, and decorin) and dentin matrix protein-1 (DMP1, a mechanosensory/osteocyte marker), while osteoblast markers, bone sialoprotein and osteopontin, remained unchanged. Disruption of homeostasis was further evidenced by increased expression of receptor-activator of nuclear factor-κB ligand (RANKL) and elevated numbers of osteoclasts, especially noted around the alveolar bone of molars (buccal side) and incisors. Polymerase chain reaction (PCR) array revealed hyperactive transforming growth factors beta/bone morphogenetic protein (TGFβ/BMP) signaling in dKO PDL tissues, which was further confirmed by elevated expression of phosphorylated Smad5 (p-Smad5) by IHC in dKO PDL. These studies highlight the importance of SLRPs in maintaining periodontal homeostasis through regulation of TGFβ/BMP signaling, matrix turnover, and collagen organization.
    Journal of Dental Research 06/2014; · 4.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: It is known that periodontal ligament (PDL) harbors a heterogeneous progenitor cell population at different stages of lineage commitment. However, characterization of PDL stem cells (PLDSCs) committed to osteoblast/cementoblast differentiation remains to be elucidated. The present study was carried out to isolate single-cell-derived PDL-CD105(+) clones and to characterize the clones that present high potential to differentiate towards osteoblast/cementoblast (O/C) phenotype in vitro. Methods: Isolation of single-cell-derived colonies (clones) from a CD105-enriched PDL progenitor cell population was performed by 'ring-cloning' technique. Cell clones were evaluated for their O/C differentiation potential, metabolic activity, and expression of STRO-1 protein. Additionally, the clones that showed potential to O/C differentiation were characterized by quantitative reverse transcription polymerase chain reaction (qRT-PCR) for expression of runt-related transcriptor factor-2 (RUNX2), alkaline phosphatase (ALP), CD105 and CD166 during osteogenic induction. Results: Six PDL-CD105(+) clones were obtained, being three highly O/C clones, namely C-O, and three others that did not have the ability to produce mineralized matrix in vitro, namely C-F. The C-O group showed lower metabolic activity compared to the C-F group, and both cell groups were positively immunostained for STRO-1. qRT-PCR analysis demonstrated an increased expression of transcripts for RUNX2 and CD166 during the maturation of C-O cells towards O/C phenotype. Conclusion: These results provide evidence that PDL-CD105(+) purified progenitor cells comprise a heterogeneous cell population, which presents a cell subset with high O/C potential, and further surface antigen CD166 is modulated during the O/C maturation of this cell subset.
    Journal of Periodontology 02/2014; · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)2D3 (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1, were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types, while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)-DLAM-2P confirmed that VDR pathway activation was required for this response. Further analysis showed that histone deacetylase recruitment was necessary, but neither protein kinase A nor C pathways were required. In conclusion, our results support the hypothesis that 1,25D regulates DMP-1 expression through a VDR-dependent mechanism, possibly contributing to local changes in bone/tooth mineral homeostasis.
    Journal of dental research 12/2013; · 4.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Psychological stress and clinical hypercortisolism have been related to direct effects on bone metabolism. However, there is a lack of information regarding the outcomes of regenerative approaches under the influence of chronic stress (CS). Enamel matrix derivative (EMD) have been used in periodontal regenerative procedures resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of CS in the rat model. Material and Methods: Twenty Wistar rats were randomly assigned to two groups: G1= CS - chronic stress (restraint stress for 12 hours/day) (n=10), G2= non-exposed to CS (n=10). Fifteen days after initiation of CS, fenestration defects were created at the buccal aspect of the first mandibular molar of all animals from both groups. After the surgeries the defects of each animal were randomly assigned to two subgroups: non-treated control and treated with EMD. The animals were euthanized 21 days later. Results: G1 showed less bone density (BD) compared to G2. EMD provided an increased defect fill (DF) in G1 and higher BD and new cementum formation (NCF) in both groups. The number of tartrate-resistant acid phosphatase-positive osteoclasts (TRAP) was significantly higher in G1 when compared to G2 and in EMD-treated sites of both groups. Conclusion: Chronic stress may produce a significant detrimental effect on bone density. EMD may provide greater defect fill when compared to non-treated control in the presence of CS and increased bone density and cementum formation in the presence or absence of CS.
    Journal of Periodontology 11/2013; · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dental cementum (DC) is a bone-like tissue covering the tooth root and responsible for attaching the tooth to the alveolar bone (AB) via the periodontal ligament (PDL). Studies have unsuccessfully tried to identify factors specific to DC versus AB, in an effort to better understand DC development and regeneration. The present study aimed to use matched human DC and AB samples (n=7) to generate their proteomes for comparative analysis. Bone samples were harvested from tooth extraction sites, whereas DC samples were obtained from the apical root portion of extracted third molars. Samples were denatured, followed by protein extraction reduction, alkylation and digestion for analysis by nanoAcquity HPLC system and LTQ-FT Ultra. Data analysis demonstrated that a total of 318 proteins were identified in AB and DC. In addition to shared proteins between these tissues, 105 and 83 proteins exclusive to AB or DC were identified, respectively. This is the first report analyzing the proteomic composition of human DC matrix and identifying putative unique and enriched proteins in comparison to alveolar bone. These findings may provide novel insights into developmental differences between DC and AB, and identify candidate biomarkers that may lead to more efficient and predictable therapies for periodontal regeneration. Periodontal disease is a highly prevalent disease affecting the world population, which involves breakdown of the tooth supporting tissues, the periodontal ligament, alveolar bone, and dental cementum. The lack of knowledge on specific factors that differentiate alveolar bone and dental cementum limits the development of more efficient and predictable reconstructive therapies. In order to better understand cementum development and potentially identify factors to improve therapeutic outcomes, we took the unique approach of using matched patient samples of dental cementum and alveolar bone to generate and compare a proteome list for each tissue. A potential biomarker for dental cementum was identified, superoxide dismutase 3 (SOD3), which is found in cementum and cementum-associated cells in mouse, pig, and human tissues. These findings may provide novel insights into developmental differences between alveolar bone and dental cementum, and represent the basis for improved and more predictable therapies.
    Journal of proteomics 09/2013; · 5.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate, clinically and histometrically, the effects of subgingival placement of a resin-modified glass-ionomer restoration during flap surgery. Nine dogs were included in this study. The mandibular canines were randomly assigned to receive either a transgingival resin-modified glass-ionomer restoration (test group) or no restoration (control group). The apical margins of the restorations in the test group and a reference notch on those in the control group were placed at the level of the bone crest. Clinical parameters were recorded 7 days before sacrifice. The dogs were sacrificed after 107 days, and undecalcified sections were obtained for histologic evaluation. Clinically, both groups presented significant clinical attachment loss and an increase in probing depth, but differences between groups were not statistically significant (P > .05). Histologically, a significant difference between groups was observed for length of epithelium (test, 4.05 ± 0.57 mm; control, 3.36 ± 0.63 mm; P = .01). The test group showed more bone resorption (2.02 ± 1.47 mm) when compared with the control group (0.74 ± 0.37 mm) (P = .048). It can be concluded that even with the claimed favorable properties of resin-modified glass ionomer, the presence of the restoration within the biologic width causes increased migration of the apical epithelium and bone resorption.
    The International journal of periodontics & restorative dentistry. 09/2013; 33(5):679-687.
  • Brian L Foster, Francisco H Nociti, Martha J Somerman
    [Show abstract] [Hide abstract]
    ABSTRACT: Teeth are mineralized organs comprised of three unique hard tissues, enamel, dentin, and cementum, and supported by the surrounding alveolar bone. While odontogenesis differs from osteogenesis in several respects, tooth mineralization is susceptible to similar developmental failures as bone. Here we discuss conditions fitting under the umbrella of "rickets," which traditionally referred to skeletal disease associated with vitamin D deficiency, but has been more recently expanded to include newly identified factors involved in endocrine regulation of vitamin D, phosphate, and calcium, including phosphate regulating endopeptidase homolog, X-linked (PHEX), fibroblast growth factor 23 (FGF23), and dentin matrix protein 1 (DMP1). Systemic mineral metabolism intersects with local regulation of mineralization, and factors including tissue nonspecific alkaline phosphatase (TNAP) are necessary for proper mineralization, where rickets can result from loss of activity of TNAP. Individuals suffering from rickets often bear the additional burden of a defective dentition, and transgenic mouse models have aided in understanding the nature and mechanisms involved in tooth defects, which may or may not parallel rachitic bone defects. This report reviews dental effects of the range of rachitic disorders, including discussion of etiologies of hereditary forms of rickets, a survey of resulting bone and tooth mineralization disorders, and a discussion of mechanisms, known and hypothesized, involved in the observed dental pathologies. Descriptions of human pathology are augmented by analysis of transgenic mouse models, and new interpretations are brought to bear on questions of how teeth are affected under conditions of rickets. In short, the "rachitic tooth" will be revealed.
    Endocrine reviews 08/2013; · 19.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this clinical trial was to assess the performance of a full-mouth ultrasonic debridement protocol in the treatment of severe chronic periodontitis in comparison with scaling and root planing in a quadrant-wise procedure in smokers. The trial consisted of 30 participants presenting with periodontitis divided into 3 groups: Group FMUD - full-mouth ultrasonic debridement, i.e., one session of 45 minutes of ultrasonic instrumentation for smokers (n = 10), Group SRP- scaling and root planing performed in a quadrant-wise manner for smokers (n = 10), and Group Control - SRP for nonsmokers (n = 10), treated following the same protocol as the SRP group. The parameters evaluated were: plaque/bleeding on probing indices, probing pocket depth, relative recession, and relative probing attachment level at baseline, 45, 90 and 180 days after therapy. Full-mouth ultrasonic debridement and scaling and root planing resulted in comparable gain of attachment 6 months after therapy. Both groups exhibited probing pocket depth reduction at all experimental periods as compared to baseline. Smokers, however, had less probing pocket depth reduction and relative probing attachment level gain compared to non-smokers, despite the mechanical protocol used (p < 0.05). Moreover, at 180 days, nonsmokers presented with fewer sites requiring re-treatment (probing pocket depth > 5 mm and bleeding on probing) than smokers (p < 0.05). Full-mouth ultrasonic debridement and scaling and root planing result in comparable clinical outcomes for the treatment of smokers with severe chronic periodontitis. Despite the non-surgical technique used, smokers had a less favorable clinical response than non-smokers.
    Journal of the International Academy of Periodontology 07/2013; 15(3):83-90.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing of ALPL identified two genetic alterations in the probands, including a heterozygous missense mutation c.454C>T, leading to change of arginine 152 to cysteine (p.R152C), and a novel heterozygous gene deletion c.1318_1320delAAC, leading to the loss of an asparagine residue at codon 440 (p.N440del). Clinical identification of low serum TNAP activity, dental abnormalities, and pedigree data strongly suggest a genotype-phenotype correlation between p.N440del and odonto-HPP in this family. Computational analysis of the p.N440del protein structure revealed an alteration in tertiary structure affecting the collagen-binding site (loop 422-452), which could potentially impair the mineralization process. Nevertheless, the Probands (compound heterozygous: p.[N440del];[R152C]) feature early-onset and severe odonto-HPP phenotype, whereas the father (p.[N440del];[=]) has only moderate symptoms, suggesting p.R152C may contribute or predispose to a more severe dental phenotype in combination with the deletion. These results assist in defining the genotype-phenotype associations for odonto-HPP, and further identify the collagen-binding site as a region of potential structural importance for TNAP function in the biomineralization.
    Bone 06/2013; · 4.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: To investigate the effect of photodynamic therapy (PDT) as adjunct to mechanical therapy in furcations. MATERIALS AND METHODS: A double-blind, parallel, randomized controlled clinical trial was conducted in subjects presenting class II furcations. The subjects were randomly allocated to a test (PDT; n = 16) or control group (non-activated laser/only photosensitizer; n = 21). At baseline, 3 and 6 months, clinical, microbiological and cytokine pattern evaluation was performed. Clinical attachment level was defined as the primary outcome variable. RESULTS: Clinical parameters improved after both therapies (p < 0.05) with no differences between groups at any time point (p > 0.05). At 6 months, real-time PCR evaluation showed a decrease in Porphyromonas gingivalis and Tannerella forsythia only in the PDT group (p < 0.05) with no inter-group differences. Regarding cytokines, IL-4 and IL-10 levels increased in both groups at 6 months. GM-CSF, IL-8, IL-1β and IL-6 levels decreased only in the PDT group after 3 months (p < 0.05). At 3 months, inter-group analyses showed that GM-CSF, IFN-γ, IL-6 and IL-8 levels were lower in the PDT group. At 6 months, lower IL-1β levels were also observed in the PDT group (p < 0.05). CONCLUSION: Photodynamic therapy did not promote clinical benefits for class II furcations; however, advantages in local levels of cytokines and a reduction in periodontopathogens were demonstrated.
    Journal Of Clinical Periodontology 05/2013; · 3.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ((-/-)) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp(-/-) mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp(-/-) mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp(-/-) mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function.
    Journal of dental research 11/2012; · 4.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Diabetes Mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues resulting in impaired periodontal repair. There is a lack of information about the outcomes of regenerative approaches under the influence of DM. Enamel matrix derivative (EMD) have been used in periodontal regenerative procedures resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of DM. Material and Methods: Twenty Wistar rats were randomly assigned to two groups: G1=DM was induced with a single intraperitoneal injection of streptozotocin (STZ) (n=10); G2= non-exposed to DM (n=10). Seven days after DM induction, bilateral fenestration defects were created at the buccal aspect of the first mandibular molar. After the surgeries the defects of each animal were randomly assigned to two subgroups: non-treated control and treated with EMD. The animals were euthanized 21 days later and the percentage of defect fill, density of newly formed bone, and new cementum formation were histometrically assessed. The number of osteoclasts was determined by tartrate-resistant acid phosphatase. Weight and glucose were also analyzed. Mann Whitney test was used for comparison between groups and Wilcoxon for comparison between the start and end times (weigh and glucose) and between treatments (cementum formation and number of osteoclasts). One-way analysis of variance was used to the defect fill and bone density. Tukey test was used when the analysis of variance test detected significant differences. (α = 5%). Results: G1 (DM) showed less defect fill and bone density (BD) compared to G2. EMD provided an increased defect fill in both groups and enhanced BD and new cementum formation only in G2. The number of tartrate-resistant acid phosphatase-positive osteoclasts was significantly higher in EMD-treated sites of G1. Conclusion: DM may produce a significant detrimental effect on bone density. EMD may provide greater defect fill under diabetic or normal conditions; however, it may not significantly increase new cementum formation in diabetic animals.
    Journal of Periodontology 11/2012; · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: This study evaluated the effect of fluoride and non-fluoride sealants on hardness decrease (HD) and marginal adaptation (MA) on enamel substrates after cariogenic challenge. METHODS: Occlusal enamel blocks, from human third molars, were randomly divided into six groups (n=12), according to occlusal fissures condition (S - sound; C - caries-like lesion; CF - caries-like lesion+topical fluoride) and sealants (F - FluroShield; H - Helioseal Clear Chroma). Lesion depths were 79.3±33.9 and 61.3±23.9 for C and CF groups, respectively. Sealants were placed on occlusal surface and stored at 100% humidity (37°C; 24h/d). HD was measured by cross-sectional microhardness analysis at the sealant margin distances: -1 (under sealant), 0 (sealant margin), 1, 2 (outer sealant). Sealant MA was observed by polarized light microscopy and scored according to: 0 - failure (no sealant MA or total sealant loss); 1 - success (sealant MA present). MA and HD were analysed by ANOVA-R and mixed model analysis, respectively. RESULTS: For HD (ΔS), F values (6900.5±3686.6) were significantly lower than H values (8534.6±5375.3) regardless of enamel substrates and sealant margin distances. Significant differences were observed among sealant margin distances: -1 (5934.0±3282.6)<0 (8701.5±6175.7)=1 (8473.2±4299.4)=2 (7761.5±4035.1), regardless of sealant and substrate. MA was similar for all groups (p≥0.05). CONCLUSION: MA was not affected by sealant type or substrate condition, whereas enamel HD was favourably impacted by fluoride in the sealant. In addition, sealants were more effective as a physical barrier than as its chemical potency in reducing enamel HD. CLINICAL SIGNIFICANCE: Sealing with a fluoride material is a recommended procedure to prevent caries of occlusal permanent molars in high-caries-risk patients, even though those exhibiting white spot lesions, since the enamel hardness decrease when fluoride sealant was used in vitro.
    Journal of dentistry 10/2012; · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue-nonspecific alkaline phosphatase (TNAP) is expressed in mineralizing tissues and functions to reduce pyrophosphate (PP(i) ), a potent inhibitor of mineralization. Loss of TNAP function causes hypophosphatasia (HPP), a heritable disorder marked by increased PP(i) , resulting in rickets and osteomalacia. Tooth root cementum defects are well described in both HPP patients and in Alpl(-/-) mice, a model for infantile HPP. In Alpl(-/-) mice, dentin mineralization is specifically delayed in the root, however, reports from human HPP patients are variable and inconsistent regarding dentin defects. In the present study, we aimed to define the molecular basis for changes in dentinogenesis observed in Alpl(-/-) mice. TNAP was found to be highly expressed by mature odontoblasts, and Alpl(-/-) molar and incisor roots featured defective dentin mineralization, ranging from a mild delay to severely disturbed root dentinogenesis. Lack of mantle dentin mineralization was associated with disordered and dysmorphic odontoblasts having disrupted expression of marker genes osteocalcin and dentin sialophosphoprotein. The formation of, initiation of mineralization within, and rupture of matrix vesicles in Alpl(-/-) dentin matrix was not affected. Osteopontin (OPN), an inhibitor of mineralization that contributes to the skeletal pathology in Alpl(-/-) mice, was present in the generally unmineralized Alpl(-/-) mantle dentin at ruptured mineralizing matrix vesicles, as detected by immunohistochemistry and by immunogold labeling. However, ablating the OPN-encoding Spp1 gene in Alpl(-/-) mice was insufficient to rescue the dentin mineralization defect. Administration of bioengineered mineral-targeting human TNAP (ENB-0040) to Alpl(-/-) mice corrected defective dentin mineralization in the molar roots. These studies reveal that TNAP participates in root dentin formation and confirm that reduction of PP(i) during dentinogenesis is necessary for odontoblast differentiation, dentin matrix secretion, and mineralization. Furthermore, these results elucidate developmental mechanisms underlying dentin pathology in HPP patients, and begin to explain the reported variability in the dentin/pulp complex pathology in these patients. © 2012 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2012; · 6.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophils play an important role in periodontitis by producing nitric oxide (NO) and antimicrobial peptides, molecules with microbicidal activity via oxygen-dependent and -independent mechanisms, respectively. It is unknown whether variation in the production of antimicrobial peptides such as LL-37, human neutrophil peptides (HNP) 1-3, and NO by neutrophils influences the pathogenesis of periodontal diseases. We compared the production of these peptides and NO by lipopolysaccharide (LPS)-stimulated neutrophils isolated from healthy subjects and from patients with periodontitis. Peripheral blood neutrophils were cultured with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS), Porphyromonas gingivalis-LPS (Pg-LPS) and Escherichia coli-LPS (Ec-LPS). qRT-PCR was used to determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3 and LL-37 proteins in the cell culture supernatants were also determined by ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa-LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients stimulated with Aa-LPS. Neutrophils from periodontitis patients produced significantly higher LL-37 protein levels than neutrophils from healthy subjects when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3 production. Neutrophils from periodontitis patients cultured or not with Pg-LPS and Ec-LPS produced significantly lower NO levels than neutrophils from healthy subjects. The significant differences in the production of LL-37 and NO between neutrophils from healthy and periodontitis subjects indicate that production of these molecules might influence individual susceptibility to important periodontal pathogens.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 08/2012; 45(11):1017-24. · 1.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Casarin RCV, Barbagallo A, Meulman BT, Santos VR, Sallum EA, Nociti FH, Duarte PM, Casati MZ, Gonçalves RB. Subgingival biodiversity in subjects with uncontrolled type-2 diabetes and chronic periodontitis. J Periodont Res 2012; doi: 10.1111/j.1600-0765.2012.01498.x. © 2012 John Wiley & Sons A/S Background and Objective:  There is a bidirectional relationship between periodontal disease and type-2 diabetes mellitus (DM). Inflammatory mediators may negatively affect glycemic control, and increased glucose levels and resultant glycation end-products may alter the host response against bacterial infection. However, no agreement has been reached regarding the effect of DM on periodontal subgingival microbiota. Therefore, the purpose of the present study was to compare the subgingival biodiversity in deep periodontal pockets of subjects with chronic periodontitis and either uncontrolled type-2 diabetes or no diabetes using 16S rRNA gene cloning and sequencing. Material and methods:  Twelve subjects with uncontrolled type-2 diabetes (glycated hemoglobin > 8%) and eleven nondiabetic subjects presenting severe and generalized chronic periodontitis were selected. Subgingival biofilm from periodontal pockets > 5 mm were assessed using the 16S rRNA gene cloning and sequencing technique. Results:  Significant differences were observed in subgingival microbiota between diabetic and nondiabetic subjects. Diabetic subjects presented higher percentages of total clones of TM7, Aggregatibacter, Neisseria, Gemella, Eikenella, Selenomonas, Actinomyces, Capnocytophaga, Fusobacterium, Veillonella and Streptococcus genera, and lower percentages of Porphyromonas, Filifactor, Eubacterium, Synergistetes, Tannerella and Treponema genera than nondiabetic individuals (p < 0.05). Moreover, some phylotypes, such as Fusobacterium nucleatum, Veillonella parvula, V. dispar and Eikenella corrodens were detected significantly more often in diabetic subjects than in nondiabetic subjects (p < 0.05). Conclusion:  Subjects with uncontrolled type-2 diabetes and chronic periodontitis presented significant dissimilarities in subgingival biodiversity compared with nondiabetic subjects.
    Journal of Periodontal Research 07/2012; · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PP(i)) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (P(i)) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains unclear. In vitro analyses were used to identify mechanisms involved in HPP-associated pulp/dentin phenotypes. Primary pulp cells cultured from HPP subjects were established to assay alkaline phosphatase (ALP) activity, mineralization, and gene expression compared with cells from healthy controls. Exogenous P(i) was provided to the correct P(i)/PP(i) ratio in cell culture. HPP cells exhibited significantly reduced ALP activity (by 50%) and mineral nodule formation (by 60%) compared with the controls. The expression of PP(i) regulatory genes was altered in HPP pulp cells, including reduction in the progressive ankylosis gene (ANKH) and increased ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Odontoblast marker gene expression was disrupted in HPP cells, including reduced osteopontin (OPN), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoprotein (MEPE). The addition of P(i) provided a corrective measure for mineralization and partially rescued the expression of some genes although cells retained altered messenger RNA levels for PP(i)-associated genes. These studies suggest that under HPP conditions pulp cells have the compromised ability to mineralize and feature a disrupted odontoblast profile, providing a first step toward understanding the molecular mechanisms for dentin phenotypes observed in HPP.
    Journal of endodontics 07/2012; 38(7):907-12. · 2.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The purpose of the present study was to evaluate the esthetic outcome of four different approaches to treat gingival recession associated with non-carious cervical lesions using 2 methods of aesthetic assessment. Method: Sixty buccal gingival recessions associated with non-carious cervical lesions were included and received one of the following treatments: coronally advanced flap alone (CAF, n=15); coronally advanced flap plus a resin-modified glass ionomer restoration (CAF+R, n=15); connective tissue graft alone (CTG, n=15); connective tissue graft plus a resin-modified glass ionomer restoration (CTG+R, n=15). Three previously calibrated observers used a before-after panel to compare the esthetic outcome by modified RES scale and by a qualitative cosmetic evaluation. Result: Substantial agreement was found among the observers (k>0.79). Among the evaluated procedures, CAF+R obtained the higher mean score for both methods of analyses and CTG+R obtained the lowest ones. Many factors negatively influenced the final results, such as degree of coverage, presence of scars and restoration color alteration. Conclusion: Within the limits of the present study, it can be concluded that CAF+R may provide the best result regarding esthetic outcome. The overall cosmetic evaluation of the 4 different approaches may not appear to be related only to the degree of soft tissue coverage.
    IADR General Session 2012; 06/2012

Publication Stats

2k Citations
406.64 Total Impact Points


  • 2012–2014
    • National Institutes of Health
      • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
      Maryland, United States
  • 2012–2013
    • National Institute of Arthritis and Musculoskeletal and Skin Diseases
      Maryland, United States
  • 1998–2013
    • University of Campinas
      • Faculty of Dentistry from Piracicaba
      Conceição de Campinas, São Paulo, Brazil
  • 2011
    • Universidade do Estado do Amazonas
      Manáos, Amazonas, Brazil
    • Laval University
      • Faculté de Médecine Dentaire
      Québec, Quebec, Canada
  • 2010–2011
    • Bahiana School of Medicine and Public Health
      Bahia, Estado de Bahía, Brazil
  • 2009
    • Federal University of Maranhão
      Maranhão, Maranhão, Brazil
  • 2006–2009
    • Universidade Guarulhos
      Guarulhos, São Paulo, Brazil
  • 2008
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
    • Universidade Federal dos Vales do Jequitinhonha e Mucuri
      Tejuco, Minas Gerais, Brazil
    • CEP America
      Emeryville, California, United States
  • 2007
    • University of São Paulo
      • Ribeirão Preto School of Medicine (FMRP)
      San Paulo, São Paulo, Brazil
  • 2004–2006
    • University of Washington Seattle
      • Department of Periodontics
      Seattle, WA, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2005
    • Ministry Of Health - Kuwait
      Al Kuwayt, Al Asimah Governorate, Kuwait
  • 2003–2005
    • University of Michigan
      • School of Dentistry
      Ann Arbor, MI, United States
    • São Paulo State University
      San Paulo, São Paulo, Brazil