The removal of mineralized bone matrix as a component of skeletal modeling, remodeling and fracture healing is the responsibility of large, multinucleated giant cells termed osteoclasts. Because osteiclasts occur in low abundance in bone and cannot be grown in tissue culture, they are poor candidates for many conventional experimental techniques. Consequently, despite their indoubted importance in overall skeletal function and calcium homeostasis, relatively little is known about their essentials physiology and chemistry. To help rectify these deficiencies and to provide a new approach to exploring diseases involving osteoclast dysfuncstion (e.g. osteopetrisis, Paget's Disease), we propose to do the following: (1) DEVELOP OSTEOCLAST SPECIFIC cDNA LIBRARIES using cDNA-mRNA hybrid selection techniques and nucleotides derived from authetic osteoclases, peripheral blood monocytes (less mature, mononuclear cells belonging to the same cell family) and foreign body giant cells (multinucleated cells phenotypically similar to osteiclasts); (2) employ selected cDNA probes to (a) CHARACTERIZE THOSE mRNAs specific FOR OR CLOSELY ASSOCIATED WITH OSTEOCLASTS AND (b) ASSESS CHANGES IN OSTEOCLAST SPECIFIC/ASSSOCIATED mRNAs IN RESPONSE TO RESORPTION REGULATING EXOGENOUS AGENTS (e.g., calcitonin, vitamin D3); (3) IDENTIFY AND CHARACTERIZE cDNA CLONES CORRESPONDING TO EXTANT OSTEOCLAST and/or GIANT SPECIFIC MONOCLONAL ANTIBODIES.
