title: Targeted disruption of oncostatin M receptor results in altered hematopoiesis.
abstract: Oncostatin M (OSM) is a multifunctional cytokine that belongs to the interleukin 6 (IL-6) family. As OSM is expressed in adult as well as embryonic hematopoietic tissues, OSM has been considered to play a role in hematopoiesis. To uncover roles of OSM, we have generated mutant mice deficient in the OSM-specific receptor beta subunit (OSMR). While OSMR-/- mice were healthy and fertile, hematologic analysis of OSMR-/- mice demonstrated that the numbers of peripheral erythrocytes and platelets were reduced compared with wild-type mice. Consistent with this, progenitors of erythroid and megakaryocyte lineages were reduced in OSMR-/- bone marrow (BM), suggesting that OSM is required for the maintenance of erythroid and megakaryocyte progenitor pools in BM. To investigate whether OSM acts on the hematopoietic progenitors directly or indirectly, we performed BM transplantation experiments. The OSMR-/- mice, engrafted with wild-type BM cells, failed to produce erythrocytic and megakaryocytic progenitors to the levels in wild-type mice, indicating that OSM affects hematopoietic microenvironments. On the other hand, erythrocytic and megakaryocytic progenitors were reduced in the wild-type mice reconstituted with OSMR-/- BM cells. Thus, OSM regulates hematopoiesis in vivo by stimulating stromal cells as well as hematopoietic progenitors, in particular megakaryocytic and erythrocytic progenitors.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. tanaka@iam.u-tokyo.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiguchi
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Motoya
authors.initials: M
authors.lastname: Katsuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002452:Cell Count; D015672:Erythroid Precursor Cells; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D051379:Mice; D018345:Mice, Knockout; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology; D018121:Receptors, Cytokine / Q000235:genetics* / Q000502:physiology*; D053677:Receptors, Oncostatin M
chemical_list: C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D053683:Oncostatin M