Physiology and pathophysiology of the dentine-pulp complex in response to dentine exposure

Abstract

Therapies to promote pulp repair and regeneration after injury should be underpinned by a deep understanding of normal tissue behaviour, and cellular signalling mechanisms. The objectives of this work were to understand normal structure of the tooth and to identify changes in its cellular elements and their complex interactions in response to dentine exposure. Revisiting pulp structure and function with a range of contemporary techniques may formalize observations into new concepts of tooth physiology and pathophysiology, and reveal new opportunities for therapeutic intervention. Studies within this thesis employed rodent mandibular incisors and molars with structural and functional investigations on demineralised teeth, non-demineralised freshly extracted pulp tissues and tissue explants. Observations were made on ground sections, haematoxylin-eosin stained sections, immunohistochemically-stained sections, and on quantitative reverse transcription polymerase chain reaction (q-RT-PCR) examination of tissue explants. Complex cellular structure and heterogeneity was observed within odontoblast and subodontoblast cellular populations. Previously undescribed odontoblast processes were identified within the predentine region during crown development and in the radicular pulp after tooth development. Programmed retraction of odontoblast processes was observed after dentine exposure by cavity preparation or tooth wear. Two phases of reactionary dentine deposition (atubular followed by tubular) was identified after tooth wear. This revealed a programmed cellular defensive mechanism which lead to tissue recovery and regeneration. This process could be controlled by autocrine or paracrine signalling mechanisms, as indicated by the presence of NGF and NGFR, in addition to a complex network of CGRP-IR axons. Observations suggested revision of established hypotheses including the hydrodynamic theory of dentine sensitivity and the role of extracellular pH in biomineralisation. This hypothesis could provide coherent explanation for several well-known dental mysteries including pulp stone development, dentine sclerosis and the mode of action of high pH materials (calcium hydroxide, and hydraulic calcium silicate cements) in the repair of pulp wounds.