title: Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors.
abstract: Connexin-43 (Cx43), a gap junction protein involved in control of cell proliferation, differentiation and migration, has been suggested to have a role in hematopoiesis. Cx43 is highly expressed in osteoblasts and osteogenic progenitors (OB/P). To elucidate the biologic function of Cx43 in the hematopoietic microenvironment (HM) and its influence in hematopoietic stem cell (HSC) activity, we studied the hematopoietic function in an in vivo model of constitutive deficiency of Cx43 in OB/P. The deficiency of Cx43 in OB/P cells does not impair the steady state hematopoiesis, but disrupts the directional trafficking of HSC/progenitors (Ps) between the bone marrow (BM) and peripheral blood (PB). OB/P Cx43 is a crucial positive regulator of transstromal migration and homing of both HSCs and progenitors in an irradiated microenvironment. However, OB/P Cx43 deficiency in nonmyeloablated animals does not result in a homing defect but induces increased endosteal lodging and decreased mobilization of HSC/Ps associated with proliferation and expansion of Cxcl12-secreting mesenchymal/osteolineage cells in the BM HM in vivo. Cx43 controls the cellular content of the BM osteogenic microenvironment and is required for homing of HSC/Ps in myeloablated animals.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45267-0055, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez-Nieto
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.forename: Anja
authors.initials: A
authors.lastname: Kohler
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ghiaur
authors.forename: Eri
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Amitava
authors.initials: A
authors.lastname: Sengupta
authors.forename: Malav
authors.initials: M
authors.lastname: Madhu
authors.forename: Jorden L
authors.initials: JL
authors.lastname: Arnett
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Santho
authors.forename: Susan K
authors.initials: SK
authors.lastname: Dunn
authors.forename: Glenn I
authors.initials: GI
authors.lastname: Fishman
authors.forename: David E
authors.initials: DE
authors.lastname: Gutstein
authors.forename: Roberto
authors.initials: R
authors.lastname: Civitelli
authors.forename: Luis C
authors.initials: LC
authors.lastname: Barrio
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
authors.forename: Jose A
authors.initials: JA
authors.lastname: Cancelas
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D055153:Stem Cell Niche / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; D018031:Connexin 43; C515256:Cxcl12 protein, mouse