| First Author | Kawamori Y | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 25 | Pages | 5528-35 |
| PubMed ID | 20813899 | Mgi Jnum | J:167420 |
| Mgi Id | MGI:4868190 | Doi | 10.1182/blood-2010-04-279216 |
| Citation | Kawamori Y, et al. (2010) Role for vitamin D receptor in the neuronal control of the hematopoietic stem cell niche. Blood 116(25):5528-35 |
| abstractText | 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 beta2-adrenergic receptor (AR) agonists. While beta2-AR agonists transiently increased mRNA expression of Vdr and its downstream gene, Rankl, 1alpha,25-dihydroxyvitamin-D(3) sustained the beta2-AR-induced Rankl expression at high level by stabilizing VDR protein. These data suggest that VDR is essential for durable beta2-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. |
