Evidence map›Paper›PMID 19839776›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2010

Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells.

Woo-Kyun Kim, Vicente Meliton, Sotirios Tetradis, Gerry Weinmaster, Theodore J Hahn, Marc Carlson, Stanley F Nelson, Farhad Parhami

Open access · bronzeAbstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 46 citations in OpenAlex.

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  15. Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017
    Article
  16. Article
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  19. Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β.Proceedings of the National Academy of Sciences of the United States of America · 2012
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Woo-Kyun KimDepartment of Medicine, UCLA School of Medicine, Los Angeles, CA, USA.
Vicente Meliton
Sotirios Tetradis
Gerry Weinmaster
Theodore J Hahn
Marc Carlson
Stanley F Nelson
Farhad Parhami
University of California, Los Angeles · USVA Greater Los Angeles Healthcare System · US

Funding

UCLA OLDER AMERICANS INDEPENDENCE CENTERP30AG028748 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MOORE, ALISON AHERN · 2006 to 2017
$9.8M
Oxysterols Regulate Marrow Stromal Cell DifferentiationR01AR050426 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PARHAMI, FARHAD · 2005 to 2009
$1.6M
NIAMS NIH HHS R01 AR050426NIA NIH HHS 5P30AG028748NIA NIH HHS P30 AG028748
6 · The paper itself

Abstract

We previously reported that specific oxysterols stimulate osteogenic differentiation of pluripotent bone marrow stromal cells (MSCs) through activation of hedgehog (Hh) signaling and may serve as potential future therapies for intervention in osteopenia and osteoporosis. In this study we report that the osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic oxysterols did not. Similar observations were made when M2 cells were treated with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine blocked 20S-induced Notch target gene expression. 20S did not induce Notch target genes in Smo(-/-) mouse embryonic fibroblasts, further confirming the role of Hh signaling in 20S-induced expression of Notch target genes. Despite the inability of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was independent of canonical Notch signaling because neither 20S nor Shh induced CBF1 luciferase reporter activity or NICD protein accumulation in the nucleus, which are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1.

Indexed as

AnimalsBasic Helix-Loop-Helix ProteinsBone Marrow CellsCell Culture TechniquesCell Cycle ProteinsFibroblastsGene ExpressionHedgehog ProteinsHomeodomain ProteinsHydroxycholesterolsLiver X ReceptorsMiceOrphan Nuclear ReceptorsOsteogenesisReceptors, NotchRNA, Messenger20-hydroxycholesterolBasic Helix-Loop-Helix ProteinsCell Cycle ProteinscyclopamineHedgehog ProteinsHes1 protein, mouseHey1 protein, mouseHomeodomain ProteinsHydroxycholesterolsLiver X ReceptorsOrphan Nuclear ReceptorsReceptors, NotchRNA, MessengerShh protein, mouseTranscription Factor HES-1Veratrum Alkaloids

Identifiers

PMID19839776
PMCPMC3153332
OpenAlexW2067733386

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.