The tooth is locked in a bony crypt from which it must escape. Its eruption depends on the formation and activation of osteoclasts on the coronal surface of the tooth. Tooth eruption, thus, offers a remarkable opportunity to study the regulation of osteoclast function. Gene manipulation experiments in the mouse have shown that mice lacking PTHrP have a failure of tooth eruption. Histologically, this seems to be due to defective osteoclast activation and not to a decrease in their number. This provides a clue as to the pathways that regulate osteoclast function in the tooth, which may shed light on the biology of the osteoclast. The understanding of osteoclast regulation is crucial because a therapeutic approach to bone diseases, including osteoporosis, will remain limited as long as osteoclast regulation is an enigma. Cell culture systems were established to study the role of the two cell types surrounding the tooth (dental follicle cells and stellate reticulum cells) in osteoclast regulation. As a test of the hypothesis that osteoclast activation, but not formation, is dependent on PTHrP in the microenvironment of the tooth, the following two aims are proposed:
The first aim i s designed to examine the ability of the dental follicle with or without the stellate reticulum to support osteoclast formation and to prove that this is independent of PTHrP. The production of molecules known to support systemic osteoclast formation will also be evaluated.
The second aim i nvolves establishing the pit- formation assay and using it to demonstrate that dental follicle cells are able to produce an osteoclast-activating molecule when pretreated with PTHrP. In the longer term, characterization of the presumed osteoclast-activating molecule will be attempted to pave the way for cloning it.
| German, Rebecca Z; Crompton, A W; Gould, Francois D H et al. (2017) Animal Models for Dysphagia Studies: What Have We Learnt So Far. Dysphagia 32:73-77 |
