Notch signaling enhances osteogenic differentiation while inhibiting adipogenesis in primary human bone marrow stromal cells

Fernando Ugarte, Martin Ryser, Sebastian Thieme, Fernando A Fierro, Katrin Navratiel, Martin Bornhäuser, Sebastian Brenner

Research output: Contribution to journalArticle

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Abstract

Objective: The Notch signaling pathway has been shown to play a role in bone marrow-derived stromal cell differentiation, however, the precise outcome of Notch activation remains controversial. The aim of this study was to evaluate the effect of Notch signaling in primary human bone marrow-derived stromal cells (hBMSCs). Materials and Methods: hBMSCs were transduced to >90% with lentiviral vectors containing either human notch1 intracellular domain (NICD), jagged1, or dominant negative mastermind1. Cells were exposed to adipogenic and osteogenic differentiation stimuli and differentiation was quantified by oil red or alizarin red staining, alkaline phosphatase liver/bone/kidney (ALPL) activity and expression of adipogenic or osteogenic marker genes. Results: NICD and jagged1 transgene-expressing hBMSCs demonstrated enhanced mineralization, nodule formation, and ALPL activity in osteogenic differentiation media. These findings correlated with increased gene expression of bone morphogenetic protein 2 and ALPL. In contrast, NICD or jagged1 transgene expression strongly inhibited adipocyte formation and reduced peroxisome proliferator-activated receptor-γ, fatty acid binding protein 4, and adiponectin precursor gene expression. Co-overexpression of dominant negative mastermind1 and NICD or jagged1 led to a partial rescue of the differentiation phenotypes. In addition, high endogenous jagged1 expression levels were observed in hBMSCs samples with strong ALPL activity compared to a group of samples with low ALPL activity. Conclusion: In summary, our data suggest that induction of Notch signaling enhances the osteogenic differentiation of hBMSCs while inhibiting the adipogenic fate.

Original languageEnglish (US)
JournalExperimental Hematology
Volume37
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

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Adipogenesis
Mesenchymal Stromal Cells
Alkaline Phosphatase
Kidney
Bone and Bones
Liver
Transgenes
Gene Expression
Fatty Acid-Binding Proteins
Bone Morphogenetic Protein 2
Peroxisome Proliferator-Activated Receptors
Phosphoprotein Phosphatases
Adiponectin
Adipocytes
Cell Differentiation
Oils
Staining and Labeling
Phenotype
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Notch signaling enhances osteogenic differentiation while inhibiting adipogenesis in primary human bone marrow stromal cells. / Ugarte, Fernando; Ryser, Martin; Thieme, Sebastian; Fierro, Fernando A; Navratiel, Katrin; Bornhäuser, Martin; Brenner, Sebastian.

In: Experimental Hematology, Vol. 37, No. 7, 07.2009.

Research output: Contribution to journalArticle

Ugarte, Fernando ; Ryser, Martin ; Thieme, Sebastian ; Fierro, Fernando A ; Navratiel, Katrin ; Bornhäuser, Martin ; Brenner, Sebastian. / Notch signaling enhances osteogenic differentiation while inhibiting adipogenesis in primary human bone marrow stromal cells. In: Experimental Hematology. 2009 ; Vol. 37, No. 7.
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