Evidence map›Paper›PMID 26056071›Full record

ArticleScientific reports2015

Osteocyte specific responses to soluble and mechanical stimuli in a stem cell derived culture model.

William R Thompson, Gunes Uzer, Kaitlyn E Brobst, Zhihui Xie, Buer Sen, Sherwin S Yen, Maya Styner, Janet Rubin

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Article
  3. Loss of the auxiliary αJBMR plus · 2024
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  6. The skeleton in a physical world.Experimental biology and medicine (Maywood, N.J.) · 2022
    Review
  7. Osteocytes and Estrogen Deficiency.Current osteoporosis reports · 2021
    Review
  8. Article
  9. The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Article
  10. Article
  11. Cell Sources for Human In vitro Bone Models.Current osteoporosis reports · 2021
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
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  19. Article
  20. Review
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.

William R ThompsonDepartment of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN 46202.
Gunes UzerDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
Kaitlyn E BrobstDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
Zhihui XieDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
Buer SenDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
Sherwin S YenDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
Maya StynerDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
Janet RubinDepartment of Medicine, University of North Carolina, Chapel Hill, NC 27599.
University of North Carolina at Chapel Hill · USIndiana University Indianapolis

Funding

UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNITP30DK056350 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SUSAN M. SMITH · 1999 to 2026
$31.6M
ELECTRIC FIELD ATTENUATION OF OSTEOCLAST FORMATIONR01AR042360 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 1993 to 2013
$2.8M
Mechanical Control of Mesenchymal Stem Cell Lineage AllocationR01AR056655 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 2010 to 2014
$1.4M
Harnessing mechanical signals to control mesenchymal stem cell fateR01EB014351 · NIBIB · STATE UNIVERSITY NEW YORK STONY BROOK · PI JUDEX, STEFAN, RUBIN, CLINTON T · 2012 to 2014
$1.0M
Role of C/EBPbeta in mechanical regulation of MSC potentialK08AR062097 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STYNER, MAYA SHALEV · 2012 to 2016
$651k
Biophysical regulation of bone remodelingR56AR042360 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 2008 to 2008
$289k
Role of mechanically activated Src/mTORC2 signaling on cytoskeletal adaptationF32AR064133 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI THOMPSON, WILLIAM ROY · 2013 to 2014
$95k
NIAMS NIH HHS AR042360NIAMS NIH HHS AR056655NIAMS NIH HHS AR064133NIAMS NIH HHS F32 AR064133NIAMS NIH HHS K08 AR062097NIAMS NIH HHS R01 AR042360NIAMS NIH HHS R01 AR056655NIAMS NIH HHS R56 AR042360NIBIB NIH HHS EB014351NIBIB NIH HHS R01 EB014351
6 · The paper itself

Abstract

Studying osteocyte behavior in culture has proven difficult because these embedded cells require spatially coordinated interactions with the matrix and surrounding cells to achieve the osteocyte phenotype. Using an easily attainable source of bone marrow mesenchymal stem cells, we generated cells with the osteocyte phenotype within two weeks. These "stem cell derived-osteocytes" (SCD-O) displayed stellate morphology and lacunocanalicular ultrastructure. Osteocytic genes Sost, Dmp1, E11, and Fgf23 were maximally expressed at 15 days and responded to PTH and 1,25(OH)2D3. Production of sclerostin mRNA and protein, within 15 days of culture makes the SCD-O model ideal for elucidating regulatory mechanisms. We found sclerostin to be regulated by mechanical factors, where low intensity vibration significantly reduced Sost expression. Additionally, this model recapitulates sclerostin production in response to osteoactive hormones, as PTH or LIV repressed secretion of sclerostin, significantly impacting Wnt-mediated Axin2 expression, via β-catenin signaling. In summary, SCD-O cells produce abundant matrix, rapidly attain the osteocyte phenotype, and secrete functional factors including sclerostin under non-immortalized conditions. This culture model enables ex vivo observations of osteocyte behavior while preserving an organ-like environment. Furthermore, as marrow-derived mesenchymal stem cells can be obtained from transgenic animals; our model enables study of genetic control of osteocyte behaviors.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAxin Proteinbeta CateninCell LineDNA-Binding ProteinsFibroblast Growth Factor-23GlycoproteinsIntercellular Signaling Peptides and ProteinsMaleMesenchymal Stem CellsMiceMice, Inbred C57BLOsteocytesSignal TransductionAdaptor Proteins, Signal TransducingAxin2 protein, mouseAxin Proteinbeta CateninDNA-Binding ProteinsFGF23 protein, humanFgf23 protein, mouseFibroblast Growth Factor-23GlycoproteinsINIP protein, humanIntercellular Signaling Peptides and ProteinsSost protein, mouse

Identifiers

PMID26056071
PMCPMC4460727
OpenAlexW570158762

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.