Mononuclear phagocytes appear to play a central and complex role in the mechanisms of bone resorption. Evidence exists that they may be precursor for the osteoclast, act independent of theosteoclast as a bone resorbing cell, or serve as an auxiliary to the osteoclast in the process of bone resorption. We have reasoned that whatever role or roles that the mononuclear phagocyte serves, there is likely to be a mechanism which acts in recruiting these cells to bone to participate in its resorption. In previous work, we have provided evidence for such a mechanism and have demonstrated the existence of a bone-derived chemotactic factor (BDCF) for macrophages. The presence of this factor(s) in organ cultured mouse bone and their media seem to be related to the degree of bone resorption in cultures.
The specific aim of this proposal is to conduct further studies on the nature of BDCF and its complexity. We shall isolate and purify the factor(s) responsible for BDCF activity, characterize its cellular response, develop immunochemical or other sensitive methods for studying its origin and synthesis in bone organ and cell cultures and study its mechanism of action in relationship to bone resorption. BDCF appears to be a part of a locally mediated mechanism bone which regulates the recruitment to mononuclear phagocytes to participate in its resorption. Thus, the ability to measure its presence and regulate its synthesis or release could provide important diagnostic and therapeutic approaches to the treatment of pathologic bone destruction in disease states such as chronic periodontitis.
