The effects of transplantation of granulocyte-macrophage progenitors on bone resorption in osteopetrotic rats

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Abstract
Osteopetrosis in the ia (incisors absent) rat is the result of reduced bone resorption due to abnormal osteoclasts. This mutant and others have been used to determine the precursor(s) to osteoclasts. Hemopoietic stem cells, isolated from bone marrow of normal littermates, cure the skeletal sclerosis and result in the formation of normal osteoclasts when transplanted into ia rats. These studies were conducted to define further the precursor to the osteoclast by evaluating the effects of the transplantation of granulocyte-macrophage progenitors on bone resorption in the ia rat. Granulocyte-colony forming cells (G-CFC), granulocyte-macrophage-colony forming cells (GM-CFC), and macrophage-colony forming cells (M-CFC) were isolated from normal bone marrow using an FITC-labeled monoclonal antibody directed against rat Thy-1.1 and fluorescence-activated cell sorting. The isolates were evaluated in soft agar culture; granulocyte isolates generated 71% G-CFC of all colonies formed and were enhanced 27 times over unfractionated cells. Mixed isolates generated 57% GM-CFC of all colonies formed and were 15 times enhanced, while macrophage isolates were 75% M-CFC with an enhancement factor of 18. The isolated populations were injected into 3-week-old ia recipients and evaluated for the ability of these cellular isolates to correct the bone resorption defect by measuring the size of the tibial marrow cavity and by identifying morphologically normal osteoclasts. In addition, isolated populations of cells were labeled with FITC and injected into ia donors to determine if labeled osteoclasts developed. G-CFC isolates, which apparently contained osteoclast precursors that were co-purified with the G-CFC, were effective in correcting the skeletal defect and giving rise to FITC-labeled osteoclasts; GM-CFC were intermediate in their effect; and M-CFC were ineffective in both curing the osteopetrotic condition and giving rise to labeled osteoclasts.
Funding Information
  • US Public Health Ser-vice (DE 06065)
  • National Institute of Dental Re-search