Osteoclastic acid ATPase: biochemical and histochemical studies of the osteopetrotic mutations in the rat.

We have used a recently described acid ATPase assay in a histochemical and biochemical analysis of osteoclast development in the three osteopetrotic mutations in the rat where bone resorption is reduced but osteoclast numbers vary, depending upon the mutation. Enzymatic activity in bone was elevated in one mutation, severely reduced in another and moderately reduced in a third. Histochemical studies confirmed that the skeletal activity resided primarily in osteoclasts and showed that the enzyme activity in the mutation with moderately reduced levels was inversely distributed between osteoclasts and mononuclear cells. Enzyme activity in spleen, liver and peritoneal macrophages was not different in mutants and normal littermates. These results represent the first biochemical correlation of previous histochemical data and underscore the heterogeneity of osteopetrotic mutations. These data suggest that acid ATPase is a characteristic but not exclusive osteoclast marker which appears in skeletal sites late in osteoclast ontogeny.