Title: 0158 - Matrix-Metalloproteinase-13 Deletion Reduces Dentine and Enamel Volume, but Increases Dystrophic-Pulp-Calcification
Hal Duncan (Presenter)
Dublin Dental University Hospital, Trinity College Dublin, University of Dublin
Yoshifumi Kobayashi, Rutgers School of Dental Medicine
Nicola Partridge, New York University
Teruyo Nakatani, New York University
Emi Shimizu, Rutgers School of Dental Medicine
Objectives: Matrix-metalloproteinase-13 (Mmp13) is important in bone formation/remodelling and dental-pulp-mineralisation. Mmp13-expression is repressed by histone-deacetylase (HDAC) 4 in bone and increased by HDAC-inhibition in dental-pulp-cell cultures, while Mmp13-inhibition affects dental-pulp-cell repair processes in vitro; however, little is known about the dental-role of Mmp13 in vivo. The aim was to investigate the role of Mmp13/collagenase-3 in tooth development and relationship with mineralisation-associated class-2 HDAC-expression.
Methods: Homozygous Mmp13-deficient mice (Mmp13−/−) on a C57BL/6 background were sacrificed at various time-points and compared with wild-type (WT) mice. The jaws were fixed, decalcified, paraffin-embedded and sectioned (5μm), prior to haematoxylin/eosin (H&E) and immunohistochemical (IHC) staining. Mmp13 expression was analysed at 1, 3, 6, 9 and 11 days post-natal, before assessment of odontoblast markers (Nestin, DSP), Mmp9, HDAC4 and 5 in similar sections at 10days and 12wks. MicroCT was used for quantitative analysis of enamel/dentine volumes in developing and mature teeth (3 month-old, male mice) and statistically analysed using a 2-sample student t-test (p<0.05).
Results: Mmp13 was highly expressed in oral-mucosa, pulp-tissue, ameloblasts and odontoblasts at all time-points; however, there was reduced expression in mature odontoblasts. Dental-hard-tissue in Mmp13-deleted mice was phenotypically normal, but the expression of Mmp9, HDAC5 and DSP was decreased compared with control. HDAC4 and 5 expression was high in odontoblasts in developing teeth, but reduced in adult samples. Pulp-stone-formation was frequently present in adult Mmp13-KO teeth (incisor/molar), but was rarely evident in WT equivalents. Enamel (p=0.045) and dentine (p=0.0003) volume was significantly reduced (13%/16% respectively) in adult Mmp13-KO samples, while animal-weight, mineral-density and total-pulp-volume was unchanged.
Conclusions: Mmp13-deficient mice exhibit a normal dental-phenotype in developing and adult teeth, but a reduced enamel and dentine volume compared with WT mice. Dystrophic pulp calcification was a frequent finding in Mmp13 groups, but not in WT-controls suggestive of a role for Mmp13 in the organisation of mineralisation in the tooth.
This abstract is based on research that was funded entirely or partially by an outside source:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE