title: CD200 expression in human cultured bone marrow mesenchymal stem cells is induced by pro-osteogenic and pro-inflammatory cues.
abstract: Similar to other adult tissue stem/progenitor cells, bone marrow mesenchymal stem/stromal cells (BM MSCs) exhibit heterogeneity at the phenotypic level and in terms of proliferation and differentiation potential. In this study such a heterogeneity was reflected by the CD200 protein. We thus characterized CD200(pos) cells sorted from whole BM MSC cultures and we investigated the molecular mechanisms regulating CD200 expression. After sorting, measurement of lineage markers showed that the osteoblastic genes RUNX2 and DLX5 were up-regulated in CD200(pos) cells compared to CD200(neg) fraction. At the functional level, CD200(pos) cells were prone to mineralize the extra-cellular matrix in vitro after sole addition of phosphates. In addition, osteogenic cues generated by bone morphogenetic protein 4 (BMP4) or BMP7 strongly induced CD200 expression. These data suggest that CD200 expression is related to commitment/differentiation towards the osteoblastic lineage. Immunohistochemistry of trephine bone marrow biopsies further corroborates the osteoblastic fate of CD200(pos) cells. However, when dexamethasone was used to direct osteogenic differentiation in vitro, CD200 was consistently down-regulated. As dexamethasone has anti-inflammatory properties, we assessed the effects of different immunological stimuli on CD200 expression. The pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α increased CD200 membrane expression but down-regulated osteoblastic gene expression suggesting an additional regulatory pathway of CD200 expression. Surprisingly, whatever the context, i.e. pro-inflammatory or pro-osteogenic, CD200 expression was down-regulated when nuclear-factor (NF)-κB was inhibited by chemical or adenoviral agents. In conclusion, CD200 expression by cultured BM MSCs can be induced by both osteogenic and pro-inflammatory cytokines through the same pathway: NF-κB.
authors.affiliation: EA3855, Université François Rabelais, Tours, France.|Department of Hematology, University Hospital of Heraklion, Heraklion, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pontikoglou
authors.affiliation: Etablissement Français du sang Centre-Atlantique, Tours, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Langonné
authors.affiliation: Stromalab Université de Toulouse, UMR/CNRS 5273, U1031 Inserm, EFS-Pyrénées-Méditerranée, UPS, Toulouse, France.
authors.forename: Mamadou Aliou
authors.initials: MA
authors.lastname: Ba
authors.affiliation: Stromalab Université de Toulouse, UMR/CNRS 5273, U1031 Inserm, EFS-Pyrénées-Méditerranée, UPS, Toulouse, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Varin
authors.affiliation: Service d'orthopédie et traumatologie, CHU Trousseau, Chambray-lès-Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rosset
authors.affiliation: Inserm U972 and Université Paris XI, Villejuif Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charbord
authors.affiliation: Stromalab Université de Toulouse, UMR/CNRS 5273, U1031 Inserm, EFS-Pyrénées-Méditerranée, UPS, Toulouse, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Sensébé
authors.affiliation: Stromalab Université de Toulouse, UMR/CNRS 5273, U1031 Inserm, EFS-Pyrénées-Méditerranée, UPS, Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Deschaseaux
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology; D061251:Primary Cell Culture; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D050659:Core Binding Factor Alpha 1 Subunit; C100596:DLX5 protein, human; D018398:Homeodomain Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D010710:Phosphates; C493709:RUNX2 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; C042739:antigens, CD200
keywords: NF-κB; cell cultures; differentiation; heterogeneity; mesenchymal stem/stromal cells; osteoblasts