As a step toward better understanding the role of inflammation in bone resorption, our objectives are: a) to characterize in detail the ultrastructure of bone resorption induced by an inflammatory infiltrate and by known stimulators of bone resorption and b) to further elucidate the role played by lysosomes in the physiology and pathology of bone resorption. There are no in vivo studies of the ultrastructure of bone resorption induced by an inflammatory infiltrate. These studies gain relevance in light of recent evidence suggesting that cells associated with inflammation are capable of stimulating bone resorption. Therefore, a thorough fine structure characterization of bone resorption induced by inflammation appears warranted. During the last few years, several stimulators of bone resorption have been isolated and partially characterized. Two of these, osteoclast activating factor and prostaglandin E2, may play key roles in stimulating bone resorption induced by an inflammatory infiltrate. We plan to introduce these stimulators into a bone organ culture system in order to characterize morphologically the bone resorbing activities of these agents. It has been shown that, when parathyroid hormone is used to stimulate bone resorption in culture, the cells remain viable and synthesize lysosomal enzymes which are then released to the exterior. This enzyme secretion is correlated with the degradation of organic matrix. We feel it is important that similar studies be performed with agents that may play a role in local inflammatory bone destruction, i.e., OAF and PGE2.
NIH ExPorter
NIH ExPorter