Evidence for a relationship between lymphoid cells and osteoclasts: Bone resorption restored in ia (osteopetrotic) rats by lymphocytes, monocytes and macrophages from a normal littermate

Osteopetrosis in the ia rat is known to be due to reduced bone resorption and the absence of ruffled borders in osteoclasts. The disease can be cured by the temporary parabiotic union with, or by transfusion of spleen, thymus, or liver cells from, normal littermates. This investigation was pursued in an attempt to determine the cellular basis of this cure by testing the relative effectiveness of populations of mononuclear cells — lymphocytes, monocytes, and tissue macrophages, from spleen and thymus of normal rats — in curing the disease, compared with cell suspensions of the entire organs. The mononuclear fractions were separated from cell suspensions of spleen or thymus by an adaptation of the Ficoll‐Hypaque density‐gradient‐centrifugation procedure. The mononuclear isolates were evaluated by conventional histological procedures and non‐specific esterase histochemistry and found to contain approximately 97% lymphocytes and 3% monocytes from the spleen and 99% lymphocytes and less than 1% monocytes from the thymus. The results of these transplantations were evaluated radiographically and histologically three weeks after treatment. No difference in the rate of skeletal cure was observed in the ia rats that received cells from either whole spleen or thymus, or the mononuclear isolate from these organs. Osteoclasts from the ia animals cured by the transplantation of the mononuclear isolate were examined by electron microscopy and found to have ruffled borders. We conclude that the mononuclear cells isolated from either the spleen or thymus of normal littermates have positive effects on osteoclasts and bone resorption in the ia rat, either indirectly, by elaboration of some local factor that affects the mutant osteoclasts, or directly by transformation into osteoclasts.