Role for vitamin D receptor in the neuronal control of the hematopoietic stem cell niche

Blood. 2010 Dec 16;116(25):5528-35. doi: 10.1182/blood-2010-04-279216. Epub 2010 Sep 2.


Hematopoietic stem/progenitor cells (HSPCs) are released from the bone marrow to the circulation by the cytokine, granulocyte colony-stimulating factor, via sympathetic nervous system (SNS)-mediated osteoblast suppression. Because the orientation of HSPCs in their osteoblastic niche is reported to be guided by [Ca(2+)], we speculated on a cooperation between the calcium-regulating hormones and SNS in the regulation of HSPC trafficking. Here, we present the severe impairment of granulocyte colony-stimulating factor-induced osteoblast suppression and subsequent HSPC mobilization in vitamin D receptor (VDR)-deficient mice. In osteoblasts, functional VDR possessing, at least in part, a transcriptional activity, was specifically induced by β2-adrenergic receptor (AR) agonists. While β2-AR agonists transiently increased mRNA expression of Vdr and its downstream gene, Rankl, 1α,25-dihydroxyvitamin-D(3) sustained the β2-AR-induced Rankl expression at high level by stabilizing VDR protein. These data suggest that VDR is essential for durable β2-AR signaling in the stem cell niche. Our study demonstrates not only a novel function of VDR as a critical modulator of HSPC trafficking, but also the presence of a SNS-mediated, bone-remodeling mechanism through VDR. VDR contributes to brain-bone-blood integration in an unanticipated way distinct from other classical calcium-regulating hormones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agonists / pharmacology
  • Animals
  • Blotting, Western
  • Calcium / administration & dosage
  • Cell Movement
  • Chemokine CXCL12 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells / physiology*
  • Leukocyte Common Antigens / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • RNA, Messenger / genetics
  • Receptors, Adrenergic, beta-1 / chemistry
  • Receptors, Calcitriol / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stem Cell Niche / physiology*
  • Sympathetic Nervous System / metabolism*
  • Vitamin D / analogs & derivatives
  • Vitamin D / pharmacology


  • Adrb1 protein, mouse
  • Adrenergic Agonists
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • RANK Ligand
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Calcitriol
  • Tnfsf11 protein, mouse
  • dihydroxy-vitamin D3
  • Vitamin D
  • Granulocyte Colony-Stimulating Factor
  • Leukocyte Common Antigens
  • Ptprc protein, mouse
  • Calcium