Open AccessCD200 expression in human cultured bone marrow mesenchymal stem cells is induced by pro‐osteogenic and pro‐inflammatory cues
Author(s) -
Pontikoglou Charalampos,
Langonné Alain,
Ba Mamadou Aliou,
Varin Audrey,
Rosset Philippe,
Charbord Pierre,
Sensébé Luc,
Deschaseaux Frédéric
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12752
Subject(s) - mesenchymal stem cell , lineage markers , microbiology and biotechnology , runx2 , biology , progenitor cell , stromal cell , stem cell , bone marrow , cellular differentiation , bone morphogenetic protein 2 , osteoblast , immunology , cancer research , in vitro , biochemistry , gene
Similar to other adult tissue stem/progenitor cells, bone marrow mesenchymal stem/stromal cells ( BM MSC s) exhibit heterogeneity at the phenotypic level and in terms of proliferation and differentiation potential. In this study such a heterogeneity was reflected by the CD 200 protein. We thus characterized CD 200 pos cells sorted from whole BM MSC cultures and we investigated the molecular mechanisms regulating CD 200 expression. After sorting, measurement of lineage markers showed that the osteoblastic genes RUNX 2 and DLX 5 were up‐regulated in CD 200 pos cells compared to CD 200 neg fraction. At the functional level, CD 200 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 ( BMP 4) or BMP 7 strongly induced CD 200 expression. These data suggest that CD 200 expression is related to commitment/differentiation towards the osteoblastic lineage. Immunohistochemistry of trephine bone marrow biopsies further corroborates the osteoblastic fate of CD 200 pos cells. However, when dexamethasone was used to direct osteogenic differentiation in vitro , CD 200 was consistently down‐regulated. As dexamethasone has anti‐inflammatory properties, we assessed the effects of different immunological stimuli on CD 200 expression. The pro‐inflammatory cytokines interleukin‐1β and tumour necrosis factor‐α increased CD 200 membrane expression but down‐regulated osteoblastic gene expression suggesting an additional regulatory pathway of CD 200 expression. Surprisingly, whatever the context, i.e . pro‐inflammatory or pro‐osteogenic, CD 200 expression was down‐regulated when nuclear‐factor ( NF )‐κB was inhibited by chemical or adenoviral agents. In conclusion, CD 200 expression by cultured BM MSC s can be induced by both osteogenic and pro‐inflammatory cytokines through the same pathway: NF ‐κB.