title: Osteomyelosclerosis, anemia and extramedullary hematopoiesis in mice lacking the transcription factor NFATc2.
abstract: BACKGROUND
  Nuclear factors of activated T cells (NFAT) are transcription factors that are central to cytokine production in activated T cells and regulate the development and differentiation of various tissues. NFATc2 is expressed in hematopoietic stem cells and regulated during myeloid commitment in a lineage-specific manner. The biological role of NFATc2 in hematopoiesis is, however, unclear.
  
  
  METHODS
  In the present study, we analyzed steady-state hematopoiesis in young (<3 months) and old (>12 months) mice lacking NFATc2. Complete blood counts were performed in the peripheral blood, bone marrow and spleen. Using cytological and histological analyses, the blood cell differential was determined. Colony-formation assays were used to determine the differentiation potential of hematopoietic cells. Bone cell cultures were derived from the bone marrow, and bone remodeling markers were determined in the serum.
  
  
  RESULTS
  NFATc2(-/-) mice older than 12 months were anemic and thrombocytopenic. The bone marrows of these mice showed a markedly reduced number of hematopoietic cells, of which megakaryocytic and erythroid lineages were most affected. While the number of hematopoietic progenitor cells in NFATc2-deficent bone marrow was reduced, the myeloid differentiation potential of these cells remained intact. Aged NFATc2(-/-) mice showed ossification of their bone marrow space and developed extramedullary hematopoiesis in the spleen. Ex vivo differentiation assays revealed an intrinsic defect of NFATc2-deficient stromal cells, in which NFATc2(-/-) osteoblasts differentiated more efficiently than wild-type cells, whereas osteoclast differentiation was impaired.
  
  
  CONCLUSIONS
  Our data suggest that NFATc2 may play a role in the maintenance of steady-state hematopoiesis and bone remodeling in adult organisms.
authors.affiliation: Department of Medicine I, Technical University Dresden, Dresden, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bauer
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.forename: Satu
authors.initials: S
authors.lastname: Kujawski
authors.forename: Laleh S
authors.initials: LS
authors.lastname: Arabanian
authors.forename: Ivonne
authors.initials: I
authors.lastname: Habermann
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiani
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000740:Anemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse