BONE CELLS AND BONE RESORPTION 491 



ous resorptive stimuli might act through "regulator" genes, which, 

 by controlling the acti\ ity of sexeral functionalh' related "structural" 

 genes, could facilitate the evocation of integrated, complex cellular 

 responses by relatively simple microenvironmenfal modifications 

 (Young, 1963Z?). 



By microen\ironment is implied the entire complex of physical 

 and chemical factors which impinge upon an individual cell. The 

 functional specialization of individual bone cells is largely deter- 

 mined by the microen\'ironment in which they are situated ( Bassett, 

 1962; Young, 1963a, 1963/?). The central region of the metaphyseal 

 trabeculae, for example, represents a microenvironment which elicits 

 activation of the osteogenic complex, whereas conditions at the distal 

 extremity of these trabeculae predispose the affected cells to resorp- 

 tion. At the overlapping edges of these microenvironmental "fields," 

 intermediate cell t\'pes are found. These are apparently osteoblasts 

 which are "de-specializing," as they come under the influence of the 

 advancing resorptive field (cf. Young, 1962a). 



Bone as a tissue provides a complex system of multitudinous, 

 graded microenvironments. A systemic stimulus to resorption, such 

 as parathvroid hormone, probablv accentuates the tendency of these 

 varied microen\'ironments to elicit the resorptive capacities of the 

 involved cells. The initial response to raised hormone levels would 

 presumably be an increase in resorptive rate by cells already en- 

 gaged in resorption. Prolongation or accentuation of this stimulus 

 would lead to an activation of the resorptive complex in cells at the 

 periphery of existing resorptive fields. Such systemic resorptive stim- 

 uli would also modifv normally osteogenic microenvironmental 

 fields, slowing bone formation, and in extreme cases ultimately 

 leading to its cessation. 



Summary 



Analvsis of bone and calcified cartilage by a variety of techniques 

 has made possible the identification of calcified matrices varying in 

 age, degree of calcification, histological organization, and chemical 

 composition. None of these variable features proved to be critical 

 in determining sites of preferential resorption in normal young rats. 



