Piper, Kim Mary; (1995) A study of the functional significance of the number of nuclei in osteoclasts. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The thesis examines first whether cell fusion confers a disproportionate advantage upon osteoclasts. Resorption pits produced by chick osteoclasts cultured on dentine were measured by confocal reflection microscopy and the size of each pit related to the number of nuclei of the osteoclast that had made it. A high correlation was found between the number of nuclei per cell and the volume of tissue resorbed. When the amount of tissue resorbed was expressed per nucleus, a trend for the larger cells to be less efficient was seen. The effect of the bisphosphonate 3-amino-1-hydroxypropylidene-1,1-bisphosphonate(APD) on chick osteoclasts of known nuclear number cultured on dentine or plastic was tested. The distribution of the nuclei was similar in the control and treated osteoclasts, suggesting that there was no preferential effect of the bisphosphonate on one size of cell more than another. The bisphosphonate in the medium inhibited resorption in a dose-related manner. The largest reduction in pit size occurred when the substrate was pre-treated with the bisphosphonate The results support the view that bisphosphonate released during resorption acts as a metabolic inhibitor. Rat and chick bone cells were cultured on glass coverslips, the rat cells in the presence and absence of a bisphosphonate. The areas and volumes of the freeze dried osteoclasts were measured. The relationships between the number of nuclei, cell area and volume are shown, and the usefulness of the method to test for metabolic inhibition explored. The osteoclast population garnered from a site of very active modelling and remodelling, the growing deer antler, was characterised. A high proportion of oligonuclear (2-5 nuclei) osteoclasts suggested a very active state of osteoclastogenesis. The morphology of osteoclasts present on the parietal bone in vivo in mice and rats of different ages was investigated in order to test the hypothesis that the nuclear distribution within a population of osteoclasts indicates the state of activity of a resorption cycle. A change m both the nuclear distribution and morphology of osteoclasts with age has been shown, and the significance of this finding is discussed.

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