Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling.

Authors
  • Fulzele, Keertik
  • Krause, Daniela S
  • Panaroni, Cristina
  • Saini, Vaibhav
  • Barry, Kevin J
  • Liu, Xiaolong
  • Lotinun, Sutada
  • Baron, Roland
  • Bonewald, Lynda
  • Feng, Jian Q
  • Chen, Min
  • Weinstein, Lee S
  • Wu, Joy Y
  • Kronenberg, Henry M
  • Scadden, David T
  • Divieti Pajevic, Paola
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Feb 07, 2013
Volume
121
Issue
6
Pages
930–939
Identifiers
DOI: 10.1182/blood-2012-06-437160
PMID: 23160461
Source
Medline
License
Unknown

Abstract

Hematopoietic progenitors are regulated in their respective niches by cells of the bone marrow microenvironment. The bone marrow microenvironment is composed of a variety of cell types, and the relative contribution of each of these cells for hematopoietic lineage maintenance has remained largely unclear. Osteocytes, the most abundant yet least understood cells in bone, are thought to initiate adaptive bone remodeling responses via osteoblasts and osteoclasts. Here we report that these cells regulate hematopoiesis, constraining myelopoiesis through a Gsα-mediated mechanism that affects G-CSF production. Mice lacking Gsα in osteocytes showed a dramatic increase in myeloid cells in bone marrow, spleen, and peripheral blood. This hematopoietic phenomenon was neither intrinsic to the hematopoietic cells nor dependent on osteoblasts but was a consequence of an altered bone marrow microenvironment imposed by Gsα deficiency in osteocytes. Conditioned media from osteocyte-enriched bone explants significantly increased myeloid colony formation in vitro, which was blocked by G-CSF–neutralizing antibody, indicating a critical role of osteocyte-derived G-CSF in the myeloid expansion.

Report this publication

Statistics

Seen <100 times