Impaired osteoclast differentiation in subcutaneous implants of bone particles in osteopetrotic mutants

Because of its synchrony and relative homogeneity, the subcutaneous model of the resorption of mineral-containing, devitalized bone particles (BPs) is useful to evaluate the recruitment, differentiation, and activity of bone-resorbing, osteoclastic cells. Bone particles were prepared from normal rats or mice and were implanted in normal and osteopetrotic rats (ia, tl, op strains) or mice (mi strain). In addition, particles of microcrystalline hydroxyapatite or polymethylmethacrylate were implanted into tl and op mutants and their unaffected littermates. Non-decalcified histomorphometry of elicited tissues after 12 days revealed significantly less resorption in each mutant. Enzyme histochemical assays revealed that only normal animals showed tartrate-resistant acid phosphatase-positive cells around the BPs. In agreement with this, only normal animals showed ruffled borders against the BPs. op and tl strains were tested for generation of foreign body giant cells in response to particulate hydroxyapatite or polymethylmethacrylate and no differences were found between mutant and normal animals. These mutants appear to have intact fusion of mononuclear progenitors. These data show impaired recruitment of osteoclasts by BP implants in several rodent strains of osteopetrotic mutants.