Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling

Keertik Fulzele, Daniela S. Krause, Cristina Panaroni, Vaibhav Saini, Kevin J. Barry, Xiaolong Liu, Sutada Lotinun, Roland Baron, Lynda Bonewald, Jian Q. Feng, Min Chen, Lee S. Weinstein, Joy Y. Wu, Henry M. Kronenberg, David T. Scadden, Paola Divieti Pajevic

Research output: Contribution to journalArticle

98 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)930-939
Number of pages10
JournalBlood
Volume121
Issue number6
DOIs
StatePublished - Feb 7 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Fulzele, K., Krause, D. S., Panaroni, C., Saini, V., Barry, K. J., Liu, X., Lotinun, S., Baron, R., Bonewald, L., Feng, J. Q., Chen, M., Weinstein, L. S., Wu, J. Y., Kronenberg, H. M., Scadden, D. T., & Pajevic, P. D. (2013). Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling. Blood, 121(6), 930-939. https://doi.org/10.1182/blood-2012-06-437160