@article{9f9c6e20b7b14b50993cc2d5d3eec554,
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.",
author = "Daniel Gonzalez-Nieto and Lina Li and Anja Kohler and Gabriel Ghiaur and Eri Ishikawa and Amitava Sengupta and Malav Madhu and Arnett, {Jorden L.} and Santho, {Rebecca A.} and Dunn, {Susan K.} and Fishman, {Glenn I.} and Gutstein, {David E.} and Roberto Civitelli and Barrio, {Luis C.} and Matthias Gunzer and Cancelas, {Jose A.}",
note = "Funding Information: This work was supported by a grant from German Cancer Aid (Deutsche Krebshilfe No. 70112502). Bristol Myers Squibb financially supported the NIVAHL trial and provided the DAKO PD-L1 antibody and Autostainer Link 48. Scanning and image analysis technology was supported by the Kinderkrebsinitiative Buchholz, Holm-Seppensen. Funding Information: Conflict-of-interest disclosures: P.J.B. reports grants from Bristol Myers Squibb (BMS) during the conduct of the study; grants from Merck Sharp & Dohme (MSD) and Affimed Therapeutics; and grants, personal fees, and nonfinancial support from BMS and Takeda outside of the submitted work. U.K. reports personal fees and travel support, support in an advisory role, and speaker{\textquoteright}s honoraria from BMS during the conduct of the study, as well as personal fees from BMS outside of the submitted work. A.Z reports personal fees and nonfinancial support from Takeda and nonfinancial support from Pfizer, Novartis, Gilead Sciences, Roche, BMS, Astellas, and MSD outside of the submitted work. M.F. reports grants from BMS during the conduct of the study and personal fees from Takeda, Amgen, Celgene, and BMS outside of the submitted work. B.v.T. reports grants and nonfinancial support from BMS during the conduct of the study; personal fees from Amgen, Pfizer, Gilead Sciences, and Roche; grants, personal fees, and nonfinancial support from MSD and Takeda; and grants and nonfinancial support from Novartis outside of the submitted work. W.K. institutional grant support from Roche, Amgen, Takeda, and Regeneron outside of the submitted work. P.B. reports grants from BMS during the conduct of the study. A.E. reports grants and nonfinancial support from BMS during the conduct of the study and personal fees from Takeda, BMS, and MSD outside of the submitted work. The remaining authors report no competing financial interests.",
year = "2012",
month = jun,
day = "5",
doi = "10.1182/blood-2011-07-368506",
language = "English (US)",
volume = "119",
pages = "5144--5154",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "22",
}