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.
Ra
Jae S
JS
The Immunomodulation Research Center and Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
Broxmeyer
Hal E
HE
Kim
Myung W
MW
Han
In-Seob
IS
Choi
Seung W
SW
Kwon
Byoung S
BS
D000362:Agar / Q000494:pharmacology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006412:Hematopoietic Stem Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008969:Molecular Sequence Data; D023461:Myeloid Progenitor Cells / Q000378:metabolism*; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003470:Culture Media; D018076:DNA, Complementary; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000362:Agar