The hematogenous origin of osteoclasts: experimental evidence from osteopetrotic (microphthalmic) mice treated with spleen cells from beige mouse donors.

The excessive skeletal mass and reduced bone resorption characteristic of osteopetrosis in microphthalmic (mi) mice can be corrected by irradiation and transfer of spleen cells from a normal littermate. Osteoclasts in beige (bg) mice, a mutation without osteopetrosis, have giant lysosomal granules. These two facts were exploited to trace osteoclast lineage. Microphthalmic mice treated with whole-body irradiation and spleen cells from a beige donor resorbed the excessive skeletal mass and recovered from osteopetrosis. Furthermore, osteoclasts in treated mi mice had giant lysosomal granules and resembled those found in bg donors when examined by light and transmission electron microscopy. These data provide direct evidence for a hematogenous origin of osteoclasts in mammals.