DLX5 overexpression impairs osteogenic differentiation of human bone marrow stromal cells.
The transcription factor DLX5 belongs to a family of homeoproteins required for craniofacial morphogenesis and forebrain development. DLX5 is expressed during formation of several skeletal elements such as cartilage, teeth and bone, and its knockout causes severe craniofacial malformations with a delay in the ossification process. Bone marrow contains mesenchymal progenitor cells which may differentiate along multiple pathways, therefore representing an interesting in vitro and in vivo model to study the mesodermal lineage differentiation. Here we report the effect of DLX5 overexpression in ex vivo expanded human bone marrow stromal cells by retroviral infection on the osteogenic lineage differentiation. A reduced mineral deposition was observed in DLX5-transduced cells upon osteogenic induction in culture. When DLX5-transduced cells were implanted in immunodeficient mice, a 60% reduction in bone matrix deposition was observed, whereas the in vitro chondrogenic potential was unaffected. A quantitative gene expression study indicated that DLX5 overexpression does not affect the early osteogenic commitment of bone marrow stromal cells but prevents their terminal differentiation. This block may be mediated by the observed persistent expression of SOX2, a transcription factor known to inhibit osteogenic differentiation.
Muraglia
Anita
A
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Perera
Marzia
M
Verardo
Sara
S
Liu
Yi
Y
Cancedda
Ranieri
R
Quarto
Rodolfo
R
Corte
Giorgio
G
D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D010011:Osteocytes / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic; D055815:Young Adult
C100596:DLX5 protein, human; D018398:Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors