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

Yuriko Kawamori, Yoshio Katayama, Noboru Asada, Kentaro Minagawa, Mari Sato, Atsuo Okamura, Manabu Shimoyama, Kimie Nakagawa, Toshio Okano, Mitsune Tanimoto, Shigeaki Kato, Toshimitsu Matsui

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 [Ca2+], 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-D3 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 brainbone-blood integration in an unanticipated way distinct from other classical calcium-regulating hormones.

Original languageEnglish
Pages (from-to)5528-5535
Number of pages8
JournalBlood
Volume116
Issue number25
DOIs
Publication statusPublished - Dec 16 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kawamori, Y., Katayama, Y., Asada, N., Minagawa, K., Sato, M., Okamura, A., Shimoyama, M., Nakagawa, K., Okano, T., Tanimoto, M., Kato, S., & Matsui, T. (2010). Role for vitamin D receptor in the neuronal control of the hematopoietic stem cell niche. Blood, 116(25), 5528-5535. https://doi.org/10.1182/blood-2010-04-279216