title: Bone marrow microenvironment in an in vitro model of Gaucher disease: consequences of glucocerebrosidase deficiency.
abstract: Gaucher disease (GD) is a lysosomal storage disorder due to glucocerebrosidase (GBA) deficiency. Mechanisms leading to the emergence of hematological and skeletal manifestations observed in GD are poorly explained. Bone marrow (BM) mesenchymal stem cells (MSCs) are multipotent progenitors that participate in the regulation of bone mass. MSCs should thus represent a cell population involved in the development or progression of bone disease in GD. In a chemical model of GD obtained with Conduritol β epoxide (CBE), a specific inhibitor of GBA activity, we functionally characterized BM MSCs and specifically analyzed their capacity to differentiate into osteoblasts. GBA deficiency obtained with CBE treatment, leads to a dramatic impairment of MSCs proliferation and to morphological abnormalities. Although the capacity of MSCs to differentiate into osteoblasts was not modified, the levels of several soluble factors that regulate bone metabolism were increased in MSCs treated with CBE, compared with untreated MSCs. Moreover, addition of conditioned media from CBE-treated MSCs on monocyte-derived osteoclasts cultured on bone matrix leads to an increase of resorption areas. These data suggested that, in GD, MSCs represents a stem cell population that is likely to be involved in bone pathogenesis.
authors.affiliation: Unité de Thérapie Cellulaire, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lecourt
authors.forename: Valérie
authors.initials: V
authors.lastname: Vanneaux
authors.forename: Audrey
authors.initials: A
authors.lastname: Cras
authors.forename: Delphine
authors.initials: D
authors.lastname: Freida
authors.forename: Djazia
authors.initials: D
authors.lastname: Heraoui
authors.forename: Linda
authors.initials: L
authors.lastname: Herbi
authors.forename: Catherine
authors.initials: C
authors.lastname: Caillaud
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
authors.forename: Jérôme
authors.initials: J
authors.lastname: Larghero
mesh_terms: D001853:Bone Marrow / Q000201:enzymology*; D001862:Bone Resorption / Q000473:pathology; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D017077:Culture Media, Conditioned; D005776:Gaucher Disease / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D005962:Glucosylceramidase / Q000172:deficiency*; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008954:Models, Biological; D010006:Osteoblasts / Q000201:enzymology / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned; D007294:Inositol; D005962:Glucosylceramidase; C011423:conduritol epoxide