title: Bone morphogenetic proteins act synergistically with haematopoietic cytokines in the differentiation of haematopoietic progenitors.
abstract: We examined the effects of bone morphogenetic protein-2 (BMP-2), -3, -4, -5, -6, and -7 on the proliferation and differentiation of bone marrow CD34+ haematopoietic progenitors in semi-solid medium. The BMPs had no effect on haematopoietic colony development when added to medium containing erythropoietin (Epo) or Interleukin-3 plus Epo. Synergistic effects with the haematopoietic cytokines stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were observed. In conjunction with GM-CSF and Epo, BMP-4 increased the number of both erythroid and granulocyte/monocyte colonies formed in semi-solid medium (P<0.01). No other BMP stimulated erythroid colony development under these conditions, while BMP-3, BMP-7 (P<0.01), BMP-5, and BMP-6 (P<0.05) stimulated granulocyte/monocyte colony formation. BMP-7 acted synergistically with stem cell factor to increase granulocyte/monocyte colony formation but not erythroid colony formation. The other BMPs did not affect either erythroid or granulocyte/monocyte colony development under these conditions. These results suggest that individual BMPs form part of the complement of cytokines regulating the development of haematopoietic progenitors, and in particular, point to a role for BMP-4 in the control of definitive, as well as embryonic erythropoiesis.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA. detmer_km@mercer.edu
authors.forename: Kristina
authors.initials: K
authors.lastname: Detmer
authors.forename: Anna N
authors.initials: AN
authors.lastname: Walker
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis; D004921:Erythropoietin / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D008747:Methylcellulose / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D019089:Stem Cell Factor / Q000096:biosynthesis; D016212:Transforming Growth Factor beta
chemical_list: D018952:Antigens, CD34; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008747:Methylcellulose