BONE MORPHOGENETIC PROTEIN-INDUCED HETEROTOPIC BONE IN OSTEOPETROSIS

The objectives of the present research on the osteopetrotic mouse are to investigate the factors influencing heterotopic bone development, T he osteopetrotic mutant was deficient in macrophage colony stimulating factor and failed to activate functioning monocytes, macrophages, and osteoclasts, Macrophage colony stimulating factor deficiency also cau sed a heretofore undescribed delay in organization and absorption of h ematomas resulting from surgical operations, Surgically implanted in a heterotopic site, bone morphogenetic protein induced approximately 10 % more bone in osteopetrotic than littermate +/? mice. Radiographicall y, the heterotopic bone was at least 50% denser than new bone. The new bone was metachromatic or slightly basophilic rather than eosinophili c and undermined with large deposits of hypercalcified hypertrophic ca rtilage, Bone mineral in the osteopetrotic mouse was deposited in an a patite-like form with a higher calcium/phosphorus ratio than the bone of +/? littermates. High levels of alkaline phosphatase synthesis were sustained longer in the osteopetrotic mouse than in the +/? littermat e, Tartrate resistant acid phosphatase synthesis was almost nil in ost eopetrotic mice during the first 4 weeks, and thereafter appeared coin cidental with spontaneous remission of osteopetrosis at 6 weeks, Impla nts of the mineralized cortical bone matrix of the osteopetrotic mouse showed minimal if any bone morphogenetic protein activity of matrix o f +/? littermate or otherwise normal mice, The cause of the remission of the bone disorder in the osteopetrotic mouse is not known but is of great interest to students studying the problem of coupling of bone f ormation to bone resorption.