title: Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling.
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.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, 50 Blossom St, Thier 1101, Boston, MA 02114, USA.
authors.forename: Keertik
authors.initials: K
authors.lastname: Fulzele
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Krause
authors.forename: Cristina
authors.initials: C
authors.lastname: Panaroni
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Saini
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barry
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Sutada
authors.initials: S
authors.lastname: Lotinun
authors.forename: Roland
authors.initials: R
authors.lastname: Baron
authors.forename: Lynda
authors.initials: L
authors.lastname: Bonewald
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Wu
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kronenberg
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Paola
authors.initials: P
authors.lastname: Divieti Pajevic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000235:genetics; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D022423:Myeloid Cells / Q000378:metabolism; D038042:Myelopoiesis; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; C486030:Sost protein, mouse; D016179:Granulocyte Colony-Stimulating Factor; D019205:GTP-Binding Protein alpha Subunits, Gs