CELLULAR AND MOLECULAR STRATEGIES FOR STUDYING THE REGULATION OF BONE-RESORPTION USING THE TOOTHLESS (OSTEOPETROTIC) MUTATION IN THE RAT

The division of labor among cells of the skeleton is distinct and dive rse and the regulation of these cells is interdependent. Osteoclasts a re the cellular source of bone resorption and signals for their develo pment and activation come, at least in part, from bone and other cells in the local environment, Studies of isolated cells have identified s ome factors in the developmental cascade of osteoclasts but there is l ittle understanding of the sequence and local concentrations, not to m ention other factors, needed for both the development of competent ost eoclasts and for coordinated bone resorption. We review the skeletal b iology of one osteopetrotic mutation in the rat, toothless, in which b one resorption is severely reduced because of a failure in the develop ment and function of osteoclasts. Furthermore, we review the advantage s and limitations of a relatively new method, differential display of mRNA (DD), that identifies differences in gene expression in two or mo re populations of cells. We present a strategy and preliminary data fo r the application of DD to this mutation, We propose that application of this method to these and other skeletal diseases, with the appropri ate controls and confirmations, will provide data about pathogenetic p athways and has a high probability for identifying new regulators of s keletal development and turnover.