Adrenomedullin in dental tissues

Musson, David (2010). Adrenomedullin in dental tissues. University of Birmingham. Ph.D.

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Abstract

Tooth development is complex and dependent on epithelial-mesenchymal interactions involving key molecular signalling pathways. Preliminary data indicate that the pleiotropic growth factor adrenomedullin (ADM) is expressed during tooth development. Furthermore, in osteoblasts, cells which share structural and functional similarities to odontoblasts, ADM increases proliferation in vitro and can promote mineralised bone volume and strength in vivo. Immunohistochemical analysis of ADM demonstrated expression during key stages in tooth development in particular in cells responsible for signalling odontoblast differentiation and subsequently in secretory odontoblasts. Similarities with the temporo-spatial expression profile of TGF-β1 were also observed. In vitro analysis using the developmentally derived dental cell lines, MDPC-23 and OD-21, demonstrated ADM stimulated a biphasic response in dental cell numbers with peak stimulation at 10-11M and that it stimulated mineral deposition at levels comparable to that of the known mineralising agent dexamethasone. Analysis of tooth tissue volume and key mandibular measurements in Swiss mice systemically treated with ADM using techniques including micro-Computer Tomography did not identify significant differences in craniofacial mineralised tissue structures compared to sham treated controls. The data presented here along with the known pleiotropic properties of ADM indicate it may be an important regulator of tooth development particularly in the processes of cell proliferation, differentiation and mineralisation. However, in adult animals systemic ADM supplementation appears to have limited affect on mandibular bone and dentine synthesis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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