Studies of the mechanism of spleen cell cure for osteopetrosis in ia rats: appearance of osteoclasts with ruffled borders.

After ia (osteopetrotic) rats receive whole body radiation and an injection of spleen cells from a normal littermate, the dense, sclerotic skeleton characteristic of osteopetrosis is rapidly remodeled and becomes normal in appearance radiographically and histologically within three weeks. The mechanism of this skeletal transformation has been explored in cured ia rats by light and electron microscopic examination of osteoclasts. In ia rats less than 25 days of age, osteoclasts viewed by electron microscopy lack a ruffled border - the extensive elaboration of plasma membrane next to the bone surface. Cured ia rats have osteoclasts with ruffled borders indistinguishable from those of normal littermates. In ia rats that receive only 600 rads whole body radiation, osteoclasts are still present three weeks later, but appear abnormal by light microscopy, with dense nuclei and lacking cytoplasmic vacuoles next to the bone surface. Cured ia rats have two types of osteoclasts, one type indistinguishable from osteoclasts of normal littermates by light microscopy, the other resembling osteoclasts of ia rats that received radiation only. These data indicate that the mechanism of the spleen cell cure for osteopetrosis in ia rats is rapid remodeling of the skeleton produced by osteoclasts with ruffled borders. Whether normal spleen cells produce these osteoclasts directly by cell division or indirectly by elaboration of some unknown local factor required for formations of ruffled borders by ia osteoclasts is not known.