Evidence map›Paper›PMID 24720889›Full record

ArticleJournal of biomechanics2014

Integrative transcriptomic and proteomic analysis of osteocytic cells exposed to fluid flow reveals novel mechano-sensitive signaling pathways.

Peter M Govey, Jon M Jacobs, Susan C Tilton, Alayna E Loiselle, Yue Zhang, Willard M Freeman, Katrina M Waters, Norman J Karin, Henry J Donahue

Abstract read
In one paragraph

Article in Journal of biomechanics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line.Laboratory investigation; a journal of technical methods and pathology · 2021
    Article
  10. Mechanosensitive miR-100 coordinates TGFβ and Wnt signaling in osteocytes during fluid shear stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  11. Review
  12. Fluid shear stress generates a unique signaling response by activating multiple TGFβ family type I receptors in osteocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  13. Review
  14. Article
  15. Article
  16. Mechanical loading disrupts osteocyte plasma membranes which initiates mechanosensation events in bone.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018
    Article
  17. Article
  18. Bone Homeostasis and Repair: Forced Into Shape.Current rheumatology reports · 2015
    Review
  19. Article
  20. Article
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

9 authors at 3 institutions in 1 country.

Peter M GoveyDivision of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, PA 17033, USA.
Jon M JacobsBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Susan C TiltonBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Alayna E LoiselleDivision of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, PA 17033, USA.
Yue ZhangDivision of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, PA 17033, USA.
Willard M FreemanDepartment of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
Katrina M WatersBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Norman J KarinBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Henry J DonahueDivision of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, PA 17033, USA. Electronic address: hdonahue@psu.edu.
Pacific Northwest National Laboratory · USPenn State Milton S. Hershey Medical Center · USPennsylvania State University · US

Funding

GAP JUNCTIONS AND BONE CELL RESPONSE TO PHYSICAL SIGNALSR01AG013087 · NIA · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI DONAHUE, HENRY J · 1994 to 2010
$2.5M
Gap Junction and Bone Cell Response to Physical SignalsR01AR068132 · NIAMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI DONAHUE, HENRY J · 2014 to 2019
$1.5M
NIAMS NIH HHS R01 AR068132NIA NIH HHS R01 AG013087NIA NIH HHS R01AG13087-15
6 · The paper itself

Abstract

Osteocytes, positioned within bone׳s porous structure, are subject to interstitial fluid flow upon whole bone loading. Such fluid flow is widely theorized to be a mechanical signal transduced by osteocytes, initiating a poorly understood cascade of signaling events mediating bone adaptation to mechanical load. The objective of this study was to examine the time course of flow-induced changes in osteocyte gene transcript and protein levels using high-throughput approaches. Osteocyte-like MLO-Y4 cells were subjected to 2h of oscillating fluid flow (1Pa peak shear stress) and analyzed following 0, 2, 8, and 24h post-flow incubation. Transcriptomic microarray analysis, followed by gene ontology pathway analysis, demonstrated fluid flow regulation of genes consistent with both known and unknown metabolic and inflammatory responses in bone. Additionally, two of the more highly up-regulated gene products - chemokines Cxcl1 and Cxcl2, supported by qPCR - have not previously been reported as responsive to fluid flow. Proteomic analysis demonstrated greatest up-regulation of the ATP-producing enzyme NDK, calcium-binding Calcyclin, and G protein-coupled receptor kinase 6. Finally, an integrative pathway analysis merging fold changes in transcript and protein levels predicted signaling nodes not directly detected at the sampled time points, including transcription factors c-Myc, c-Jun, and RelA/NF-κB. These results extend our knowledge of the osteocytic response to fluid flow, most notably up-regulation of Cxcl1 and Cxcl2 as possible paracrine agents for osteoblastic and osteoclastic recruitment. Moreover, these results demonstrate the utility of integrative, high-throughput approaches in place of a traditional candidate approach for identifying novel mechano-sensitive signaling molecules.

Indexed as

Gene Expression RegulationSignal TransductionStress, MechanicalAnimalsBone and BonesCell LineChemokine CXCL1Chemokine CXCL2Gene Expression ProfilingInflammationMiceOsteocytesPolymerase Chain ReactionProteinsProteomeChemokine CXCL1Chemokine CXCL2Cxcl1 protein, mouseCxcl2 protein, mouseProteinsProteomeFluid flowMechanotransductionOsteocyteShear stressSignaling

Identifiers

PMID24720889
PMCPMC4037855
OpenAlexW1998646078

What OpenQuestion holds

Textmetadata
LicenceTDM
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.