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Molecular Oral Pathophysiology

Oral diseases are a major health concern. These-ones are extremely frequent due to a cumulative number of different origins. They constitute co-morbidity factors of the systemic diseases affecting modern populations. The resulting functional handicap impacts individual quality of life. Finally, the ensuing treatment costs are high.


  Our team explores oral physiology and pathology from bench to bedside. Our goal is to identify and characterize distinct molecular pathways driving jaw-tooth biology by focusing on exemplary inherited and environmental dysfunctions and oral reconstruction process. To do so, the team generates and uses original cell and animal models of oral development, diseases and repair. The team manages, annotates large human patient cohorts and tissue libraries. Finally, our Cordeliers Research Center team federates networks centered on the University of Paris health and dental school, notably a platform (tissue/mineral investigation from the anatomical to nanoscale levels) « InterMinD », the HEADNECK national oral rare disease network (part of European ERN Action) as well as cross-talks with dental industries and academies for therapeutic innovations.



Organizational chart


1. Genetic diseases (A Berdal, R Kozyraki and O Cases)

In the Reference Centers ORares and Maface and the national HeadNeck Action set up and managed by our team, the team annotates the hundreds of rare diseases affecting jaws induced by gene mutations. These delineate molecular paths starting with one given oral sign and integrating other affected organs and systems, as done recently for enamel (De la Dure Molla, in press). The coming years will explore syndromes involving enamel, kidney, eyes, bone and gingiva (ectopic mineralization). We will focus on 2 pathways: (1) megalin-cubilin and their roles in cell trafficking and endocytotic diseases and (2) FAM20A, post-translational modifications of extracellular proteins and biomineralization.


2. Gene-Environment cross-talks (S Babajko)

At that time, it is assumed that Endocrine Disrupting Chemicals (EDCs) alter general health. Based on our data, they also impact oral status. Irreversible enamel defects, widespread in our modern population (fluorosis, caries and molar incisor hypomineralization affecting 15% 6-7 year-old children) would be part of EDCs exposure consequences. We aim to provide the oral profile of chemical pollutant effects from bench to bedside. We focus our in vivo and in vitro studies on 1) hormonal regulations of dental and oral development during the critical window of fetal and early post-natal life and 2) molecular mechanisms of EDCs and fluoride. We assume that the signaling pathways we will discover in dental cells intervene in other oral and extra-oral sites, explored in a network with Cordeliers Research Center and external teams.


3. Neurectomesenchyme and biotherapies (B Fournier, B Gogly, J Isaac and S Simon)

Oral mesenchymal cells are unique in the body, presumably due to their specific neuroectodermal origin. We analyze the jaw-specific fibroblast phenotype which would contribute to the unique healing « fœtal-like » properties of gingiva and the specific profile of jaw osteoblasts which would share odontoblast and mesodermal osteoblast phenotype. Our studies are testing innovative treatments for bone reconstruction and endodontics (H2020 MaxiBone & industrial projects).



Team Leader: Ariane BERDAL (PU-PH; Univ Paris Diderot) and Sylvie BABAJKO (DR; Inserm)


Team Members:

Researchers: Fleur BERES Fleur (MCU-PH; Univ Paris Descartes), Alba BOLANOS HOTTON (Prof Ass; CDD),  Olivier CASES (CR; CNRS), Beatriz CASTANEDA, (Prof Ass; CDD), Sophie DOUBLIER (Prof Ass; CDD), François  FERRE (MCU-PH; Univ Paris Descartes), Benjamin FOURNIER (MCU-PH; Univ Paris Diderot),  Bruno GOGLY (PU-PH; Univ Paris Descartes), Sophia HOUARI (MCU-PH; Univ Paris Diderot), Juliane ISAAC (MCU, Univ Paris Diderot), Natacha KADLUB (MCU-PH; Univ Paris Descartes),  Renata KOZYRAKI (CR; Inserm), Guilhem LIGNON (AA; CDD), Arnaud PICARD (PU-PH; Sorbonne Univ), Jean-Marc RICORT (PU; ENS Cachan), Stéphane SIMON (PU-PH; Univ Paris Diderot), Ihsene TAIHI (AHU; Paris Descartes), Marie Paule VAZQUEZ (PU-PH; Univ Paris Descartes).

Technical Staff: Audrey ASSELIN (AI; Univ Paris Diderot); Vidjeacoumary CANNAYA (Tec; Paris Diderot), Jocelyne EDWARDS (Adj Tec; Univ Paris Diderot), Dominique HOTTON Dominique (IR, Inserm), Sophia LOIODICE (AI; Univ Paris Diderot), Stéphane PETIT (IR; Univ Paris Diderot)

Young Researchers: Ai Thu BUI (PhD Student), Andrea GAMA DA SILVA (PhD Student), Katia JEDEON (Post-Doc), Ali NASSIF (Post-Doc), Victor SIMANCAS ESCORCIA (PhD Student).


Administration: Shu-Chiung KOVATS (Adj Tec, Univ Paris Diderot)

Team Website:




  • Merzoug-Larabi M, Youssef I, Bui AT, Legay C, Loiodice S, Lognon S, Babajko S, Ricort JM. Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells. Front Pharmacol. 2020 Jan 31;10:1683.
  • Korah L, Amri N, Bugueno IM, Hotton D, Tenenbaum H, Huck O, Berdal A, Davideau JL. Experimental periodontitis in Msx2 mutant mice induces alveolar bone necrosis. J Periodontol. 2019 Sep 30.
  • Hotton D, Berdal A, Bolaños A. Methods for In Situ Protein Visualization in Dental Mineralized Tissues. Methods Mol Biol. 2019;1922:173-180.
  • Lignon G*, Hotton D*, Berdal A, Bolaños A. In Situ Hybridization in Mineralized Tissues: The Added Value of LNA Probes for RNA Detection. Methods Mol Biol. 2019;1922:181-190.
  • Isaac J, Nassif A, Asselin A, Taïhi I, Fohrer-Ting H, Klein C, Gogly B, Berdal A, Robert B, Fournier BP. Involvement of neural crest and paraxial mesoderm in oral mucosal development and healing. Biomaterials. 2018;172:41-53.
  • Loison-Robert LS, Tassin M, Bonte E, Berbar T, Isaac J, Berdal A, Simon S, Fournier BPJ.
    In vitro effects of two silicate-based materials, Biodentine and BioRoot RCS, on dental pulp stem cells in models of reactionary and reparative dentinogenesis. PLoS One. 2018;13(1):e0190014.
  • Kadlub N, Sessiecq Q, Mandavit M, L'Hermine AC, Badoual C, Galmiche L, Berdal A, Descroix V, Picard A, Coudert AE. Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation. Orphanet J Rare Dis. 2018;13(1):166.
  • Fournier BP, Bruneau MH, Toupenay S, Kerner S, Berdal A, Cormier-Daire V, Hadj-Rabia S, Coudert AE, de La Dure-Molla M. Patterns of Dental Agenesis Highlight the Nature of the Causative Mutated Genes. J Dent Res. 2018;97(12):1306-1316.
  • Toupenay S, Fournier BP, Manière MC, Ifi-Naulin C, Berdal A, de La Dure-Molla M.
    Amelogenesis imperfecta: therapeutic strategy from primary to permanent dentition across case reports. BMC Oral Health. 2018 ;18(1):108.
  • Berès F, Lignon G, Rouzière S, Mauprivez C, Simon S, Berdal A, Dessombz A. Physicochemical analysis of human pulpal mineralization secondary to FAM20A mutations. Connect Tissue Res. 2018;59(sup1):46-51.
  • Collignon AM, Amri N, Lesieur J, Sadoine J, Ribes S, Menashi S, Simon S, Berdal A, Rochefort GY, Chaussain C, Gaucher C. Sclerostin Deficiency Promotes Reparative Dentinogenesis. J Dent Res. 2017;96(7):815-821.
  • Cases O, Obry A, Ben-Yacoub S, Augustin S, Joseph A, Toutirais G, Simonutti M, Christ A, Cosette P, Kozyraki R. Impaired vitreous composition and retinal pigment epithelium function in the FoxG1::LRP2 myopic mice. Biochim. Biophys. Acta. 2017;1863(6):1242-1254.
  • Lignon G, Berès F, Quentrick M, Rouzière S, Weil R, de la Dure-Molla M, Naveau A, Kozyraki R,  Dessombz A, Berdal A. FAM20A gene mutation : amelogenesis or ectopic mineralization ? Front. Physiol. 2017;8:267.
  • Yamaguti PM, Neves FA, Hotton D, Bardet C, de La Dure-Molla M, Castro LC, Scher MD, Barbosa ME, Ditsch C, Fricain JC, de La Faille R, Figueres ML, Vargas-Poussou R, Houiller P, Chaussain C, Babajko S, Berdal A*, Acevedo AC*. Amelogenesis imperfecta in famillial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations. J. Med. Genet., 2017; 54(1):26-37 (* co-last authors)
  • Friedlander L, Choquet R, Galliani E, de Chalendar M, Messiaen C, Ruel A, Vazquez MP, Berdal A, Alberti C, De La Dure Molla M. Management of rare diseases of the head and teeth: results of a french population-based pospective 8-yar study. Orphanet J Rare Dis. 2017;19;12(1):94
  • Sojod B, Château D, Mueller CG, Babajko S, Berdal A, Lézot F, Castaneda B. RANK/RANKL/OPG signalization implication in periodontitis: new evidence from a RANK transgenic mouse model. Front. Physiol. 2017; 8:338.
  • Zanini M, Meyer E, Simon S. Pulp inflammation diagnosis from clinical to inflammatory mediators: A systematic review. J Endod. 2017; 43(7):13033-1051.
  • Babajko S, Jedeon K, Houari S, Loiodice S, Berdal A. Disruption of steroid axis, a new paradigm for Molar Incisor Hypomineralization (MIH). Front. Physiol., 2017; 8:343.
  • Houari S, Loiodice S, Jedeon K, Berdal A, Babajko S. Expression of steroid receptors in ameloblasts during amelogenesis in rat incisors. Front. Physiol. 2016; 2;7:503.
  • Jedeon K, Loiodice S, Salhi K, Le Normand M, Houari S, Chaloyard J, Berdal A, Babajko S. Androgen receptor involment in rat amelogenesis : an additional way for endocrine-disrupting chemicals to affect enamel synthesis. Endocrinology 2016; 157(11):4287-4296
  • Jedeon K, Houari S, Loiodice S, Tran Thu T, Le Normand M, Berdal A, Babajko S. Chronic exposure to bisphenol A exacerbates dental fluorosis in growing rats. J. Bone Miner. Res., 2016; 31(11):1955-1966
  • Berès F, Isaac J, Mouton L, Rouzière S, Berdal A, Simon S, Dessombz A. Comparative physicochemical analysis of pulp stone and dentin. J. Endod 2016; 42(3):432-438.
  • Amri N, Djolé SX, Petit S, Babajko S, Coudert AE, Castaneda B, Simon S, Berdal A. Distorted patterns of dentinogenessis and eruption in Msx2 null mutants: involvement of Sost/Sclerostin. Am. J. Pathol. 2016;186(10):2577-2587. 
  • Kadlub N, Sessiecq Q, Dainese L, Joly A, Lehalle D, Marlin S, Badoual C, Galmiche L, Majoufre-Lefebvre C, Berdal A, Deckert M, Vazquez MP, Descroix V, Coudert AE, Picard A. Defining a new aggressiveness classification and using NFATc1 localization as a prognostic factor in cherubism. Hum Pathol. 2016;58:62-71.
  • Smith AJ, Diogenes A, Simon S, Cooper PR. Exploiting the Bioactive Properties of Dentin-Pulp in Regenerative Endodontics. J Endod. 2016;42(1):47-56
  • Cherifi H, Gogly B, Loison-Robert LS, Couty L, Ferré FC, Nassif A, Lafont A, Fournier BP. Comparative study of abdominal and thoracic aortic aneurysms: their pathogenesis and a gingival fibroblasts-based ex-vivo treatment. Springerplus, 2015; 4:231
  • Cases O, Joseph A, Obry A, Santin MD, Ben-Yacoub S, Pâques M, Amsellem-Levera S, Bribian A, Simonutti M, Augustin S, Debeir T, Sahel JA, Christ A, de Castro F, Lehéricy S, Cosette P, Kozyraki R. Foxg1-Cre mediated Lrp2 inactivation in the developing mouse neural retina, ciliary and retinal pigment epithelia models congenital high myopia. PloS One, 2015;10(6):e0129518
  • Kadlub N, Vazquez MP, Galmiche L, L'Herminé AC, Dainese L, Ulinski T, Fauroux B, Pavlov I, Badoual C, Marlin S, Deckert M, Leboulanger N, Berdal A, Descroix V, Picard A, Coudert AE. The calcineurin inhibitor tacrolimus as a new therapy in severe cherubism. J Bone Miner. Res., 2015; 30(5):878-885
  • De La Dure-Molla M, Fournier B, Berdal A. Isolated dentinogenesis imperfecta and dentin dysplasia : revision of the classification. Eur. J. Hum. Genet., 2015; 23(4):445-451
  • Babajko S, de La Dure-Molla M, Jedeon K, Berdal A. Msx2 in ameloblast cell fate and activity. Frontiers in Physiology, section Craniofacial Biology, 2015, 5:510
  • Lignon G, de la Dure-Molla M, Dessombz A, Berdal A, Babajko S. Enamel : A unique self-assembling in mineral world. Médecine/Sciences, 2015, 31(5):515-21
  • Isaac J, Erthal J, Gordon J, Duverger O, Sun HW, Lichtler AC, Stein GS, Lian JB, Morasso MI. DLX3 regulates bone mass by targeting genes supporting osteoblast differentiation and mineral homeostasis in vivo. Cell Death Differ. 2014;21(9):1365-76
  • De la Dure Molla M, Quentric M, Yamaguti PM, Acevedo A-C, Mighell AJ, Vikkula M, Huckert M, Berdal A, Bloch-Zupan A. Pathognomomic oral profile of enamel renal syndrome (ERS) caused by recessive FAM20A mutations. Orphanet J. Rare Dis. 2014;14(9):84
  • Nassif A, Senussi I, Meary F, Loiodice S, Hotton D, Robert B, Bensidhoum M, Berdal A, Babajko S. Msx1 role in craniofacial bone morphogenesis. Bone, 2014;66c:96-104
  • Jedeon K, Loiodice S, Marciano C, Vinel A, Canivenc-Lavier MC, Berdal A, Babajko S. Estrogen and bisphenol A affect male rat enamel formation and promote ameloblast proliferation. Endocrinology, 2014 ;155(9):3365-3375
  • Ferré F, Larjava H, Loison-Robert LS, Berbar T, Owen G, Berdal A, Chérifi H, Gogly B, Hakkinen L, Fournier BP. Formation of cartilage and synovial tissue by human gingival stem cells. Stem Cells Dev. 2014;23(23):2895-2907  
  • Häkkinen L, Larjava H, Fournier BP. Distinct phenotype and therapeutic potential of gingival fibroblasts. Cytotherapy 2014;16(9):1171-1186
  • Houari S, Wurtz T, Ferbus D, Chateau D, Dessombz A, Berdal A, Babajko S. Asporin and the mineralization process in fluoride-treated rats. J. Bone Miner. Res. 2014 29(6):1446-1455.
  • Jacques J, Hotton D, de la Dure-Molla M, Petit S, Asselin A, Kulkarni AB, Gibson CW, Brookes SJ, Berdal A, Isaac J. Tracking endogenous amelogenin and ameloblastin in vivo. PLoS One 2014;9(6): e99626
  • Häkkinen L, Larjava H, Fournier BP. Distinct phenotype and therapeutic potential of gingival fibroblasts.  Cytotherapy. 2014;16(9):1171-86.
  • Cases O, Perea-Gomez A, Aguiar DP, Nykjaer A, Amsellem S, Chandellier J, Umbhauer M, Cereghini S, Madsen M, Collignon J, Verroust P, Riou JF, Creuzet SE, Kozyraki R. Cubilin, a high affinity receptor for fibroblast growth factor 8, is required for cell survival in the developing vertebrate head. J. Biol. Chem. 2013;288(23):16655–16670
  • Storm T, Zeitz C, Cases O, Amsellem S, Verroust PJ, Madsen M, Benoist JF, Passemard S, Lebon S, Jønsson IM, Emma F, Koldsø H, Hertz JM, Nielsen R, Christensen EI, Kozyraki R. Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome. BMC Med. Genet. 2013;14:111
  • Castaneda B, Simon Y, Ferbus D, Robert B, Chesneau J, Mueller C, Berdal A, Lézot F. Role of RANKL (TNFSF11)-dependent osteopetrosis in the dental phenotype of Msx2 null mutant mice. PLoS One 2013; 8(11):e80054
  • Jedeon K, De la Dure-Molla M, Brookes SJ, Loiodice S, Marciano C, Kirkham J, Canivenc-Lavier MC, Boudalia S, Bergès R, Harada H, Berdal A, Babajko S. Enamel defects reflect perinatal exposure to bisphenol a. Am. J. Pathol. 2013; 183(1):108-118
  • Fournier BPJ, Larjava H, Häkkinen L. Gingiva as a source of stem cells with therapeutic potential. Stem Cells Dev., 2013;  22(24):3157-3177
  • Dessombz A, Nguyen C, Ea HK, Rouzière S, Foy E, Hannouche D, Réguer S, Picca FE, Thiaudière D, Lioté F, Daudon M, Bazin D. Combining μX-ray fluorescence, μXANES and μXRD to shed light on Zn2 cations in cartilage and meniscus calcifications. J. Trace Element Med. Biol. 2013; 27(4):326-333
  • Simon S, Perard M, Zanini M, Smith AJ, Charpentier E, Djole SX, Lumley PJ. Should pulp chamber pulpotomy be seen as a permanent treatment ? Some preliminary thoughts. Int. Endod J. 2013;46(1):79-87
  • Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie 2013;95(5):1002–1007
  • Fournier BPJ, Larjava H, Häkkinen L. Gingiva as a source of stem cells with therapeutic potential. Stem Cells Dev. 2013; 22(24):3157-3177

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