Evidence map›Paper›PMID 22563076›Full record

Trial reportThe Journal of biological chemistry2012

Protein kinase G and focal adhesion kinase converge on Src/Akt/β-catenin signaling module in osteoblast mechanotransduction.

Hema Rangaswami, Raphaela Schwappacher, Trish Tran, Geraldine C Chan, Shunhui Zhuang, Gerry R Boss, Renate B Pilz

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Signalling pathways underlying pulsed electromagnetic fields in bone repair.Frontiers in bioengineering and biotechnology · 2024
    Review
  8. Review
  9. Article
  10. Protein Kinase G2 Is Essential for Skeletal Homeostasis and Adaptation to Mechanical Loading in Male but Not Female Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
    Article
  11. Review
  12. 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
  13. Role of nitric oxide in orthodontic tooth movement (Review).International journal of molecular medicine · 2021
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. 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

7 authors at 1 institution in 1 country.

Hema RangaswamiDepartment of Medicine and Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Raphaela Schwappacher
Trish Tran
Geraldine C Chan
Shunhui Zhuang
Gerry R Boss
Renate B Pilz
University of California, San Diego · US

Funding

REGULATION OF GENE EXPRESSION BY cGMP and PKG IN BONER01AR051300 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PILZ, RENATE B · 2004 to 2014
$3.1M
NIAMS NIH HHS R01 AR051300NIAMS NIH HHS R01-AR051300
6 · The paper itself

Abstract

Mechanical loading of bone induces interstitial fluid flow, leading to fluid shear stress (FSS) of osteoblasts. FSS rapidly increases the intracellular calcium concentration ([Ca(2+)]) and nitric oxide (NO) synthesis in osteoblasts and activates the protein kinase Akt. Activated Akt stimulates osteoblast proliferation and survival, but the mechanism(s) leading to Akt activation is not well defined. Using pharmacological and genetic approaches in primary human and mouse osteoblasts and mouse MC3T3 osteoblast-like cells, we found that Akt activation by FSS occurred through two parallel pathways; one required calcium stimulation of NO synthase and NO/cGMP/protein kinase G II-dependent activation of Src, and the other required calcium activation of FAK and Src, independent of NO. Both pathways cooperated to increase PI3K-dependent Akt phosphorylation and were necessary for FSS to induce nuclear translocation of β-catenin, c-fos, and cox-2 gene expression and osteoblast proliferation. These data explain how mechanical stimulation of osteoblasts leads to increased signaling through a growth regulatory pathway essential for maintaining skeletal integrity.

Indexed as

Animalsbeta CateninCell LineCyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IICyclooxygenase 2FemaleFocal Adhesion Kinase 1HumansMaleMechanotransduction, CellularMiceMice, KnockoutNitric Oxide SynthasePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktbeta CateninCyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IICyclooxygenase 2Focal Adhesion Kinase 1Nitric Oxide SynthasePhosphatidylinositol 3-KinasesPRKG2 protein, humanPrkg2 protein, mouseProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-fosPTGS2 protein, humanPtgs2 protein, mousePTK2 protein, humanPtk2 protein, mousesrc-Family Kinases

Identifiers

PMID22563076
PMCPMC3375572
OpenAlexW2062939612

What OpenQuestion holds

Textmetadata
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.