title: Promyelocytic leukemia zinc-finger induction signs mesenchymal stem cell commitment: identification of a key marker for stemness maintenance?
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage and bone tissue engineering given their ability to differentiate into chondrocytes and osteoblasts. However, the common origin of these two specialized cell types raised the question about the identification of regulatory pathways determining the differentiation fate of MSCs into chondrocyte or osteoblast.
  
  
  METHODS
  Chondrogenesis, osteoblastogenesis, and adipogenesis of human and mouse MSC were induced by using specific inductive culture conditions. Expression of promyelocytic leukemia zinc-finger (PLZF) or differentiation markers in MSCs was determined by RT-qPCR. PLZF-expressing MSC were implanted in a mouse osteochondral defect model and the neotissue was analyzed by routine histology and microcomputed tomography.
  
  
  RESULTS
  We found out that PLZF is not expressed in MSCs and its expression at early stages of MSC differentiation is the mark of their commitment toward the three main lineages. PLZF acts as an upstream regulator of both Sox9 and Runx2, and its overexpression in MSC enhances chondrogenesis and osteogenesis while it inhibits adipogenesis. In vivo, implantation of PLZF-expressing MSC in mice with full-thickness osteochondral defects resulted in the formation of a reparative tissue resembling cartilage and bone.
  
  
  CONCLUSIONS
  Our findings demonstrate that absence of PLZF is required for stemness maintenance and its expression is an early event at the onset of MSC commitment during the differentiation processes of the three main lineages.
authors.forename: Farida
authors.initials: F
authors.lastname: Djouad
authors.forename: Gautier
authors.initials: G
authors.lastname: Tejedor
authors.forename: Karine
authors.initials: K
authors.lastname: Toupet
authors.forename: Marie
authors.initials: M
authors.lastname: Maumus
authors.forename: Claire
authors.initials: C
authors.lastname: Bony
authors.forename: Anne
authors.initials: A
authors.lastname: Blangy
authors.forename: Paul
authors.initials: P
authors.lastname: Chuchana
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020219:Chondrogenesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D010012:Osteogenesis; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D055758:SOX9 Transcription Factor; C092037:ZBTB16 protein, human