21 



In Vitro Studies of Bone 

 Resorptive Mechanisms 



GEORGE NICHOLS, Jh., Departments of Medicine and Biochemistry, 

 Harvard Medical School, Boston, Massachusetts 



IT IS clear that resorption of bone takes place under a variety of 

 normal and pathological circumstances; yet knowledge of the de- 

 tails of the process, its control, and its relationship to other systems 

 for the removal of unwanted tissue elements is still fragmentary. 

 Though changes in cellular morphology on the one hand and in 

 the morphology and ph\'siologv of the mineralized extracellular 

 matrix on the other have been shown to occur in bone undergoing 

 resorption, the relation between these two at the chemical level has 

 remained obscure despite extensive investigation (McLean and 

 Urist, 1961; Lacroix, 1956; Jowsey, 1960; Gaillard, 1961; Frost et 

 ah, 1960; Vincent and Haumont, 1960). 



Any comprehensive review of what has been done is beyond the 

 scope of this paper. Therefore, I shall discuss largely our own work, 

 indicating how our thinking about the chemistry of bone resorption 

 has developed, outlining the ways in which we have attempted to 

 study the process at the biochemical level, and reviewing our prog- 

 ress, such as it is, along these lines. The experiments to be described 

 began four years ago and have been carried out with a number of 

 collaborators including Drs. Nancy Nichols, Andre Borle, Stein 

 Schartum, Gilbert Vaes, Barry Flanagan, and John Woods. Without 



557 



