Polycomb Protein BMI1 Regulates Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Downstream of GSK3.
Polycomb proteins such as the B lymphoma Mo-MLV insertion region 1 homolog (BMI1) are essential chromatin factors for the self-renewal and differentiation of embryonic and adult stem cells. BMI1 also plays a critical role in osteogenesis as Bmi1-deficient mice display a skeletal phenotype caused by the exhaustion of the mesenchymal stem cell pool. In this study, we have studied the role of BMI1 in the osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). BMI1 protein, but not RNA levels, increases during in vitro osteogenic differentiation of hASCs. Overexpression of BMI1 leads to an osteogenic priming of hASCs under nondifferentiating conditions and enhanced osteogenesis upon differentiation, along with increased BMP2 and WNT11 expressions. Conversely, knockdown of BMI1 expression reduces osteogenic differentiation. Furthermore, our studies indicate that during osteogenic differentiation of hASCs, BMI1 is a downstream target of GSK3 signaling. BMI1, therefore, acts as a pro-osteogenic differentiation factor in hASCs and hence it is a promising target for active modulation of hASC-derived osteogenesis.
1 Institute for Medical Radiation and Cell Research (MSZ), Center of Experimental Molecular Medicine (ZEMM) , Würzburg, Germany .
Matthias
M
Becker
1 Institute for Medical Radiation and Cell Research (MSZ), Center of Experimental Molecular Medicine (ZEMM) , Würzburg, Germany .
Tamara
T
Potapenko
1 Institute for Medical Radiation and Cell Research (MSZ), Center of Experimental Molecular Medicine (ZEMM) , Würzburg, Germany .
Andrea
A
Niklaus
2 Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg , German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany .
Karen
K
Bieback
3 Department of Internal Medicine V, Heidelberg University Hospital , Heidelberg, Germany .
Anthony D
AD
Ho
1 Institute for Medical Radiation and Cell Research (MSZ), Center of Experimental Molecular Medicine (ZEMM) , Würzburg, Germany .
Albrecht M
AM
Müller
D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D001857:Bone Matrix / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D015398:Signal Transduction
C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1; D038362:Glycogen Synthase Kinase 3; D000469:Alkaline Phosphatase