20(S)-Hydroxycholesterol and Notch Signaling in Bone Marrow Cells
Author Information
Author(s): Kim Woo-Kyun, Meliton Vicente, Tetradis Sotirios, Weinmaster Gerry, Hahn Theodore J, Carlson Marc, Nelson Stanley F, Parhami Farhad
Primary Institution: UCLA School of Medicine
Hypothesis
Does 20(S)-hydroxycholesterol induce Notch target gene expression in bone marrow stromal cells?
Conclusion
20(S)-hydroxycholesterol induces the expression of Notch target genes in bone marrow stromal cells primarily through Hedgehog signaling.
Supporting Evidence
- 20(S)-hydroxycholesterol significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells.
- The induction of Notch target gene expression by 20S is not mediated by the canonical Notch signaling pathway.
- Cyclopamine, a Hedgehog pathway inhibitor, blocked 20S-induced Notch target gene expression.
- HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes.
Takeaway
A substance called 20(S)-hydroxycholesterol helps certain cells in our bones grow and develop by turning on specific genes, and it does this using a special signaling pathway.
Methodology
The study used mouse marrow stromal cells and examined gene expression through quantitative PCR after treatment with 20(S)-hydroxycholesterol.
Limitations
The study primarily focuses on in vitro results, which may not fully represent in vivo conditions.
Participant Demographics
Mouse bone marrow stromal cells were used in the study.
Statistical Information
P-Value
p = .0017 for HES-1 and p = .0009 for HEY-2
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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