title: Connexin43 intercellular communication drives the early differentiation of human bone marrow stromal cells into osteoblasts.
abstract: Although it has been demonstrated that human bone marrow stromal cells (hBMSCs) express the ubiquitous connexin43 (Cx43) and form functional gap junctions, their role in the early differentiation of hBMSCs into osteoblasts remains poorly documented. Using in vitro assays, we show that Cx43 expression and gap junctional intercellular communication (GJIC) are increased during the differentiation of hBMSCs into osteoblasts, both at the protein and mRNA levels. Two independent procedures to reduce GJIC, a pharmacological approach with GJIC inhibitors (18α-glycyrrhetinic acid and Gap27 peptide) and a molecular approach using small interfering RNA against Cx43, demonstrated that the presence of Cx43 and functional junctional channels are essential to the ability of hBMSCs to differentiate into osteoblasts in vitro. In addition, a reduced GJIC decreases the expression of Runx2, the major transcription factor implicated in the control of osteoblast commitment and early differentiation of hBMSCs into osteoblasts, suggesting that GJIC mediated by Cx43 is implicated in this process. Together our results demonstrate that GJIC mediated by the Cx43 channels plays a central role throughout the differentiation of hBMSC into osteoblasts, from the early stages to the process of mineralization.
authors.affiliation: INSERM, UMR 957, Nantes, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Talbot
authors.affiliation: INSERM, UMR 957, Nantes, France.|INSERM, UMR 1238, Nantes, France.|Université Bretagne Loire, Nantes, France.|CHU, Nantes, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Brion
authors.affiliation: INSERM, UMR 957, Nantes, France.|INSERM, UMR 1238, Nantes, France.|Université Bretagne Loire, Nantes, France.|CHU, Nantes, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Lamora
authors.affiliation: INSERM, UMR 957, Nantes, France.|INSERM, UMR 1238, Nantes, France.|Université Bretagne Loire, Nantes, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Mullard
authors.affiliation: INSERM, UMR 957, Nantes, France.|INSERM, UMR 1238, Nantes, France.|Université Bretagne Loire, Nantes, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Morice
authors.affiliation: INSERM, UMR 957, Nantes, France.|CHU, Nantes, France.|Department of Oncology and metabolism, INSERM European Associated Laboratory, University of Sheffield, Shefflied, UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: INSERM, UMR 957, Nantes, France.|INSERM, UMR 1238, Nantes, France.|Université Bretagne Loire, Nantes, France.
authors.forename: Franck
authors.identifier: http://orcid.org/0000-0003-4920-2554
authors.initials: F
authors.lastname: Verrecchia
mesh_terms: D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D034622:RNA Interference; D015398:Signal Transduction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D018031:Connexin 43; D017630:Connexins; C500216:GJA1 protein, human; D009842:Oligopeptides; C455880:gap 27 peptide; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid
keywords: cell differentiation; connexin43; gap junction; human bone marrow stromal cells; intercellular communication; osteoblast