Osteoprotegerin inhibits proliferation of myeloid progenitor cells

Osteoprotegerin (OPG) and decoy receptor 3 (DcR) are soluble members of the tumor necrosis factor receptor (TNFR) superfamily. Because the proteins are found in the circulation, their effect on hematopoietic progenitor cells was examined. OPG suppressed colony formation by all myeloid progenitor cells stimulated with one or more growth factors. OPG suppressed colony formation by granulocyte, granulocyte-macrophage, erythroid, and multipotential progenitors. Suppression was 64.2-35.0% of control. Although OPG and DcR3 contain approximately 43% identity and approximately 62% similar amino acids in their TNFR-motif-containing regions, DcR3 did not show any effects on hematopoietic progenitor cell proliferation. The data indicate that OPG has a broader spectrum of activity than previously defined and that myelosuppression may need to be monitored for when OPG is used clinically.