Pamela Den Besten, DDS

Professor
Orofacial Sciences

The focus of research in the Den Besten laboratory is in the biomineralization of tooth enamel and dentin. They currently have several active projects to study various aspects of enamel and dentin biomineralization. One of these projects aims to determine the mechanism by which fluoride affects enamel formation to result in enamel fluorosis. In this project they are investigating several possible mechanisms by which enamel fluorosis occurs, including altered protein/mineral interactions, and a direct of fluoride on the developing ameloblasts.

In order to determine factors that alter enamel formation, we need to better understand the proteins, proteinases and other molecules responsible for normal enamel formation. We are using immunopertrubation and antisense methods in tooth organ culture to alter the presence of certain proteins in enamel development. These studies have suggested that the enamel matrix protein, ameloblastin, has a key role in the regulation of enamel matrix synthesis.

Their studies on dentin formation have utilized various available transgenic mouse models with transgene expression driven by the osteocalcin promotor. In one of these mice models that over expresses TGF- , the dentin mineral apposition rate is increased while the physical properties of the dentin remain the same. Studies of dentin formation in these various transgenic mouse models will allow us to determine the key elements in dentin biomineralization and to use these elements to form dentin-like materials in vitro.

Interests: tooth, biomineralization

Publications: 

Fluoride exposure and blood cell markers of inflammation in children and adolescents in the United States: NHANES, 2013-2016.

Environmental health : a global access science source

Den Besten P, Wells CR, Abduweli Uyghurturk D

Culturing and Scaling up Stem Cells of Dental Pulp Origin Using Microcarriers.

Polymers

Földes A, Reider H, Varga A, Nagy KS, Perczel-Kovach K, Kis-Petik K, DenBesten P, Ballagi A, Varga G

Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation.

Frontiers in pharmacology

Földes A, Sang-Ngoen T, Kádár K, Rácz R, Zsembery Á, DenBesten P, Steward MC, Varga G

TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.

International journal of molecular sciences

Kádár K, Juhász V, Földes A, Rácz R, Zhang Y, Löchli H, Kató E, Köles L, Steward MC, DenBesten P, Varga G, Zsembery Á

Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California.

Environmental health : a global access science source

Abduweli Uyghurturk D, Goin DE, Martinez-Mier EA, Woodruff TJ, DenBesten PK

Fluoride related changes in behavioral outcomes may relate to increased serotonin.

Physiology & behavior

Lu F, Zhang Y, Trivedi A, Jiang X, Chandra D, Zheng J, Nakano Y, Abduweli Uyghurturk D, Jalai R, Onur SG, Mentes A, DenBesten PK

The Importance of Connexin 43 in Enamel Development and Mineralization.

Frontiers in physiology

Al-Ansari S, Jalali R, Plotkin LI, Bronckers ALJJ, DenBesten P, Zhang Y, Raber-Durlacher JE, de Lange J, Rozema FR

Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016.

Journal of dental research

Herzog CR, Berzins DW, DenBesten P, Gregory RL, Hargreaves KM, Messer RLW, Mina M, Mooney MP, Paine ML, Phillips C, Presland RB, Quivey RG, Scannapieco FA, Sheridan JF, Svoboda KKH, Trackman PC, Walker MP, Walker SG, Wang CY, Hu JCC

No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by Fluoride in a Novel Ameloblast Model.

Frontiers in physiology

Rácz R, Földes A, Bori E, Zsembery Á, Harada H, Steward MC, DenBesten P, Bronckers ALJJ, Gerber G, Varga G

Meeting report: a hard look at the state of enamel research.

International journal of oral science

Klein OD, Duverger O, Shaw W, Lacruz RS, Joester D, Moradian-Oldak J, Pugach MK, Wright JT, Millar SE, Kulkarni AB, Bartlett JD, Diekwisch TG, DenBesten P, Simmer JP

The Role of Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) in Dental Epithelium during Enamel Formation in Mice.

Frontiers in physiology

Jalali R, Lodder JC, Zandieh-Doulabi B, Micha D, Melvin JE, Catalan MA, Mansvelder HD, DenBesten P, Bronckers A

Corrigendum to " Mineralization-defects are comparable in fluorotic impacted human teeth and fluorotic mouse incisors" [Archives of Oral Biology 29 (July (83)) (2017) 214-221].

Archives of oral biology

Jalali R, Guy F, Ghazanfari S, Lyaruu D, van Ruijven L, DenBesten P, Martignon S, Castiblanco G, Bronckers A

Mineralization-defects are comparable in fluorotic impacted human teeth and fluorotic mouse incisors.

Archives of oral biology

Jalali R, Guy F, Ghazanfari S, Lyaruu D, van Ruijven L, DenBesten P, Martignon S, Castiblanco G, Bronckers ALJJ

Mediator 1 contributes to enamel mineralization as a coactivator for Notch1 signaling and stimulates transcription of the alkaline phosphatase gene.

The Journal of biological chemistry

Yoshizaki K, Hu L, Nguyen T, Sakai K, Ishikawa M, Takahashi I, Fukumoto S, DenBesten PK, Bikle DD, Oda Y, Yamada Y

Buffering of protons released by mineral formation during amelogenesis in mice.

European journal of oral sciences

Bronckers AL, Lyaruu DM, Jalali R, DenBesten PK

The C-terminus of amelogenin enhances osteogenic differentiation of human cementoblast lineage cells.

Journal of periodontal research

Kunimatsu R, Yoshimi Y, Hirose N, Awada T, Miyauchi M, Takata T, Li W, Zhu L, Denbesten PK, Tanimoto K

Effects of C-Terminal Amelogenin Peptide on Proliferation of Human Cementoblast Lineage Cells.

Journal of periodontology

Yoshimi Y, Kunimatsu R, Hirose N, Awada T, Miyauchi M, Takata T, Li W, Zhu L, Denbesten P, Tanne K, Tanimoto K

Ameloblast Modulation and Transport of Cl?, Na?, and K? during Amelogenesis.

Journal of dental research

Bronckers AL, Lyaruu D, Jalali R, Medina JF, Zandieh-Doulabi B, DenBesten PK

Slc26a3/Dra and Slc26a6 in Murine Ameloblasts.

Journal of dental research

Jalali R, Zandieh-Doulabi B, DenBesten PK, Seidler U, Riederer B, Wedenoja S, Micha D, Bronckers AL

Composition of mineralizing incisor enamel in cystic fibrosis transmembrane conductance regulator-deficient mice.

European journal of oral sciences

Bronckers AL, Lyaruu DM, Guo J, Bijvelds MJ, Bervoets TJ, Zandieh-Doulabi B, Medina JF, Li Z, Zhang Y, DenBesten PK

Amelogenins as potential buffers during secretory-stage amelogenesis.

Journal of dental research

Guo J, Lyaruu DM, Takano Y, Gibson CW, DenBesten PK, Bronckers AL

Distinctive genetic activity pattern of the human dental pulp between deciduous and permanent teeth.

PloS one

Kim JH, Jeon M, Song JS, Lee JH, Choi BJ, Jung HS, Moon SJ, DenBesten PK, Kim SO

NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse.

Cell and tissue research

Jalali R, Guo J, Zandieh-Doulabi B, Bervoets TJ, Paine ML, Boron WF, Parker MD, Bijvelds MJ, Medina JF, DenBesten PK, Bronckers AL

WDR72 models of structure and function: a stage-specific regulator of enamel mineralization.

Matrix biology : journal of the International Society for Matrix Biology

Katsura KA, Horst JA, Chandra D, Le TQ, Nakano Y, Zhang Y, Horst OV, Zhu L, Le MH, DenBesten PK

Barrier formation: potential molecular mechanism of enamel fluorosis.

Journal of dental research

Lyaruu DM, Medina JF, Sarvide S, Bervoets TJ, Everts V, Denbesten P, Smith CE, Bronckers AL

Inductive ability of human developing and differentiated dental mesenchyme.

Cells, tissues, organs

Zheng L, Warotayanont R, Stahl J, Kunimatsu R, Klein O, DenBesten PK, Zhang Y

Parenteral monofluorophosphate (MFP) is a more potent inducer of enamel fluorotic defects in neonatal hamster molars than sodium fluoride.

Odontology

Lyaruu DM, Schoonderwoerd M, Tio D, Tse C, Bervoets TJ, DenBesten P, Bronckers AL

Leucine rich amelogenin peptide alters ameloblast differentiation in vivo.

Matrix biology : journal of the International Society for Matrix Biology

Stahl J, Nakano Y, Kim SO, Gibson CW, Le T, DenBesten P

The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells.

International journal of oral science

Zheng LW, Linthicum L, DenBesten PK, Zhang Y

Clinical efficacy and effects of xylitol wipes on bacterial virulence.

Advances in dental research

Zhan L, Featherstone JD, Lo J, Krupansky C, Hoang N, DenBesten P, Huynh T

Effects of xylitol wipes on cariogenic bacteria and caries in young children.

Journal of dental research

Zhan L, Cheng J, Chang P, Ngo M, Denbesten PK, Hoover CI, Featherstone JD

Amelogenin exons 8 and 9 encoded peptide enhances leucine rich amelogenin peptide mediated dental pulp repair.

Cells, tissues, organs

Huang Y, Goldberg M, Le T, Qiang R, Warner D, Witkowska HE, Liu H, Zhu L, Denbesten P, Li W

Murine ameloblasts are immunonegative for Tcirg1, the v-H-ATPase subunit essential for the osteoclast plasma proton pump.

Bone

Bronckers AL, Lyaruu DM, Bervoets TJ, Medina JF, DenBesten P, Richter J, Everts V

Developmental expression of solute carrier family 26A member 4 (SLC26A4/pendrin) during amelogenesis in developing rodent teeth.

European journal of oral sciences

Bronckers AL, Guo J, Zandieh-Doulabi B, Bervoets TJ, Lyaruu DM, Li X, Wangemann P, DenBesten P

Fluoride incorporation into apatite crystals delays amelogenin hydrolysis.

European journal of oral sciences

DenBesten PK, Zhu L, Li W, Tanimoto K, Liu H, Witkowska HE

Evolutionary story of mammalian-specific amelogenin exons 4, "4b", 8, and 9.

Journal of dental research

Sire JY, Huang Y, Li W, Delgado S, Goldberg M, Denbesten PK

Chronic fluoride toxicity: dental fluorosis.

Monographs in oral science

DenBesten P, Li W

Altered self-assembly and apatite binding of amelogenin induced by N-terminal proline mutation.

Archives of oral biology

Zhu L, Uskokovic V, Le T, Denbesten P, Huang Y, Habelitz S, Li W

NBCe1 in mouse and human ameloblasts may be indirectly regulated by fluoride.

Journal of dental research

Zheng L, Zhang Y, He P, Kim J, Schneider R, Bronckers AL, Lyaruu DM, DenBesten PK

Fate of fluoride-induced subameloblastic cysts in developing hamster molar tooth germs.

Archives of oral biology

Lyaruu DM, Alberga JM, Kwee NC, Bervoets TJ, Bronckers AL, DenBesten PK

Ameloblast differentiation in the human developing tooth: effects of extracellular matrices.

Matrix biology : journal of the International Society for Matrix Biology

He P, Zhang Y, Kim SO, Radlanski RJ, Butcher K, Schneider RA, DenBesten PK

Horizontal transmission of mutans streptococci in children.

Journal of dental research

Doméjean S, Zhan L, DenBesten PK, Stamper J, Boyce WT, Featherstone JD

The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in maturation stage ameloblasts, odontoblasts and bone cells.

Bone

Bronckers A, Kalogeraki L, Jorna HJ, Wilke M, Bervoets TJ, Lyaruu DM, Zandieh-Doulabi B, Denbesten P, de Jonge H

The impact of fluoride on ameloblasts and the mechanisms of enamel fluorosis.

Journal of dental research

Bronckers AL, Lyaruu DM, DenBesten PK

Calcium-mediated differentiation of ameloblast lineage cells in vitro.

Journal of experimental zoology. Part B, Molecular and developmental evolution

Chen J, Zhang Y, Mendoza J, Denbesten P

Functional roles of prolines at amelogenin C terminal during tooth enamel formation.

Cells, tissues, organs

Zhu L, Tanimoto K, Le T, DenBesten PK, Li W

The effect of fluoride on enamel and dentin formation in the uremic rat incisor.

Pediatric nephrology (Berlin, Germany)

Lyaruu DM, Bronckers AL, Santos F, Mathias R, DenBesten P

Inflammatory and immunological aspects of dental pulp repair.

Pharmacological research

Goldberg M, Farges JC, Lacerda-Pinheiro S, Six N, Jegat N, Decup F, Septier D, Carrouel F, Durand S, Chaussain-Miller C, Denbesten P, Veis A, Poliard A

Reduced amelogenin-MMP20 interactions in amelogenesis imperfecta.

Journal of dental research

Tanimoto K, Le T, Zhu L, Witkowska HE, Robinson S, Hall S, Hwang P, Denbesten P, Li W

Comparative properties of recombinant human and bovine matrix metalloproteinase-20.

Archives of oral biology

Zhu L, Tanimoto K, Robinsin S, Chen J, Witkowska E, Hall S, Le T, Denbesten PK, Li W

Effects of fluoride on the interactions between amelogenin and apatite crystals.

Journal of dental research

Tanimoto K, Le T, Zhu L, Chen J, Featherstone JD, Li W, DenBesten P

Matricellular molecules and odontoblast progenitors as tools for dentin repair and regeneration.

Clinical oral investigations

Goldberg M, Lacerda-Pinheiro S, Priam F, Jegat N, Six N, Bonnefoix M, Septier D, Chaussain-Miller C, Veis A, Denbesten P, Poliard A

The effect of LRAP on enamel organ epithelial cell differentiation.

Journal of dental research

Le TQ, Zhang Y, Li W, Denbesten PK

Dentonin, a MEPE fragment, initiates pulp-healing response to injury.

Journal of dental research

Six N, Septier D, Chaussain-Miller C, Blacher R, DenBesten P, Goldberg M

JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro.

Matrix biology : journal of the International Society for Matrix Biology

Zhang Y, Li W, Chi HS, Chen J, Denbesten PK

Micromolar fluoride alters ameloblast lineage cells in vitro.

Journal of dental research

Yan Q, Zhang Y, Li W, Denbesten PK

Elevated TGF-beta2 signaling in dentin results in sex related enamel defects.

Archives of oral biology

Saeki K, Hilton JF, Alliston T, Habelitz S, Marshall SJ, Marshall GW, Denbesten P

Comparative calcium binding of leucine-rich amelogenin peptide and full-length amelogenin.

European journal of oral sciences

Le TQ, Gochin M, Featherstone JD, Li W, DenBesten PK

Differentiation of human ameloblast-lineage cells in vitro.

European journal of oral sciences

Yan Q, Zhang Y, Li W, DenBesten PK

Growth of ameloblast-lineage cells in a three-dimensional Matrigel environment.

European journal of oral sciences

Li W, Machule D, Gao C, DenBesten PK

Self-assembly and effect on crystal growth of the leucine-rich amelogenin peptide.

European journal of oral sciences

Habelitz S, DenBesten PK, Marshall SJ, Marshall GW, Li W

The impact of bioactive molecules to stimulate tooth repair and regeneration as part of restorative dentistry.

Dental clinics of North America

Goldberg M, Lacerda-Pinheiro S, Jegat N, Six N, Septier D, Priam F, Bonnefoix M, Tompkins K, Chardin H, Denbesten P, Veis A, Poliard A

On-column activation of bovine recombinant metalloproteinase 20.

Analytical biochemistry

Wang S, Zhu J, Zhang Y, Li L, DenBesten P, Li W

Amelogenin control over apatite crystal growth is affected by the pH and degree of ionic saturation.

Orthodontics & craniofacial research

Habelitz S, Denbesten PK, Marshall SJ, Marshall GW, Li W

Mouse amelogenin exons 8 and 9: sequence analysis and protein distribution.

Journal of dental research

Papagerakis P, Ibarra JM, Inozentseva N, DenBesten P, MacDougall M

MEPE is downregulated as dental pulp stem cells differentiate.

Archives of oral biology

Liu H, Li W, Shi S, Habelitz S, Gao C, Denbesten P

Characterization of human primary enamel organ epithelial cells in vitro.

Archives of oral biology

DenBesten PK, Machule D, Zhang Y, Yan Q, Li W

Effects of sodium fluoride on the actin cytoskeleton of murine ameloblasts.

Archives of oral biology

Li Y, Decker S, Yuan ZA, Denbesten PK, Aragon MA, Jordan-Sciutto K, Abrams WR, Huh J, McDonald C, Chen E, MacDougall M, Gibson CW

Amelogenin-guided crystal growth on fluoroapatite glass-ceramics.

Journal of dental research

Habelitz S, Kullar A, Marshall SJ, DenBesten PK, Balooch M, Marshall GW, Li W

Dentonin, a fragment of MEPE, enhanced dental pulp stem cell proliferation.

Journal of dental research

Liu H, Li W, Gao C, Kumagai Y, Blacher RW, DenBesten PK

Early childhood caries: an overview with reference to our experience in California.

Journal of the California Dental Association

DenBesten P, Berkowitz R

Effects of fluoride on rat dental enamel matrix proteinases.

Archives of oral biology

DenBesten PK, Yan Y, Featherstone JD, Hilton JF, Smith CE, Li W

Stem cell properties of human dental pulp stem cells.

Journal of dental research

Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S

Identification of the calcium-sensing receptor in the developing tooth organ.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Mathias RS, Mathews CH, Machule C, Gao D, Li W, Denbesten PK

The effect of TGF-beta 2 on dentin apposition and hardness in transgenic mice.

Advances in dental research

DenBesten PK, Machule D, Gallagher R, Marshall GW, Mathews C, Filvaroff E

Reduced hydrolysis of amelogenin may result in X-linked amelogenesis imperfecta.

Matrix biology : journal of the International Society for Matrix Biology

Li W, Gibson CW, Abrams WR, Andrews DW, DenBesten PK

Increased fluoride content in the femur growth plate and cortical bone of uremic rats.

Pediatric nephrology (Berlin, Germany)

Mathias RS, Amin U, Mathews CH, Denbesten P

Is teething associated with diarrhea?

The Western journal of medicine

DenBesten P

Development and characterization of an SV40 immortalized porcine ameloblast-like cell line.

European journal of oral sciences

DenBesten PK, Gao C, Li W, Mathews CH, Gruenert DC

Canadian Consensus Conference on the appropriate use of fluoride supplements for the prevention of dental caries in children.

Journal (Canadian Dental Association)

Limeback H, Ismail A, Banting D, DenBesten P, Featherstone J, Riordan PJ

Identification of two additional exons at the 3' end of the amelogenin gene.

Archives of oral biology

Li W, Mathews C, Gao C, DenBesten PK

Alternative splicing of amelogenin mRNA from rat incisor ameloblasts.

Journal of dental research

Li R, Li W, DenBesten PK

Purification of nonamelogenin proteins from bovine secretory enamel.

Calcified tissue international

Punzi JS, DenBesten PK

Neurotoxicity of sodium fluoride in rats.

Neurotoxicology and teratology

Mullenix PJ, Denbesten PK, Schunior A, Kernan WJ

Fluoride binding by matrix proteins in rat mineralizing tissue.

Archives of oral biology

DenBesten PK, Heffernan LM, Featherstone JD, Shields CP

Changes in the fluoride-induced modulation of maturation stage ameloblasts of rats.

Journal of dental research

Denbesten PK, Crenshaw MA, Wilson MH

The effects of chronic high fluoride levels on forming enamel in the rat.

Archives of oral biology

DenBesten PK, Crenshaw MA

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