Reduced life span of the osteoclast in osteopetrotic (mi and midi) mice.

Osteoclasts were enumerated on the parietal bones of mice carrying combinations of alleles (mi, midi and +) at the microphthalmic locus. Homozygous mutants at this locus show varying degrees of osteopetrosis due to defective bone resorption. As the severity of the bone resorption defect increased across the genotypes, there was an increase in the total number of osteoclasts and also an increase in the proportion of uninucleate osteoclasts. In parietal bones incubated for 24 h with parathyroid hormone (PTH) there was no significant difference between osteopetrotic and normal bones in terms of the number of osteoclast nuclei that had taken part in fusion. When bones were incubated for 24 h in the absence of PTH the percentage of osteoclasts remaining was correlated inversely with the severity of the bone resorption defect. Thus, we suggest that the increased proportion of uninucleate osteoclasts in these mutants results from a shortened life span, reducing the time-dependent accumulation of nuclei. This implies a reduced efficiency of uninucleate osteoclasts over multinucleate ones and we speculate on the reason for this.