Evidence map›Paper›PMID 21940634›Full record

ArticleThe Journal of biological chemistry2011

Osteopontin signals through calcium and nuclear factor of activated T cells (NFAT) in osteoclasts: a novel RGD-dependent pathway promoting cell survival.

Natsuko Tanabe, Benjamin D Wheal, Jiyun Kwon, Hong H Chen, Ryan P P Shugg, Stephen M Sims, Harvey A Goldberg, S Jeffrey Dixon

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 50 citations in OpenAlex.

  1. Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026
    Review
  2. Article
  3. Review
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  8. Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
    Article
  9. Article
  10. Osteopontin in Bone Metabolism and Bone Diseases.Medical science monitor : international medical journal of experimental and clinical research · 2020
    Review
  11. Article
  12. Article
  13. Review
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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 3 countries.

Natsuko TanabeDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London N6A5C1, Canada.
Benjamin D Wheal
Jiyun Kwon
Hong H Chen
Ryan P P Shugg
Stephen M Sims
Harvey A Goldberg
S Jeffrey Dixon
Western University · CANihon University · JP

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Osteopontin (OPN), an integrin-binding extracellular matrix glycoprotein, enhances osteoclast activity; however, its mechanisms of action are elusive. The Ca(2+)-dependent transcription factor NFATc1 is essential for osteoclast differentiation. We assessed the effects of OPN on NFATc1, which translocates to nuclei upon activation. Osteoclasts from neonatal rabbits and rats were plated on coverslips, uncoated or coated with OPN or bovine albumin. OPN enhanced the proportion of osteoclasts exhibiting nuclear NFATc1. An RGD-containing, integrin-blocking peptide prevented the translocation of NFATc1 induced by OPN. Moreover, mutant OPN lacking RGD failed to induce translocation of NFATc1. Thus, activation of NFATc1 is dependent on integrin binding through RGD. Using fluorescence imaging, OPN was found to increase the proportion of osteoclasts exhibiting transient elevations in cytosolic Ca(2+) (oscillations). OPN also enhanced osteoclast survival. The intracellular Ca(2+) chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) suppressed Ca(2+) oscillations and inhibited increases in NFATc1 translocation and survival induced by OPN. Furthermore, a specific, cell-permeable peptide inhibitor of NFAT activation blocked the effects of OPN on NFATc1 translocation and osteoclast survival. This is the first demonstration that OPN activates NFATc1 and enhances osteoclast survival through a Ca(2+)-NFAT-dependent pathway. Increased NFATc1 activity and enhanced osteoclast survival may account for the stimulatory effects of OPN on osteoclast function in vivo.

Indexed as

Active Transport, Cell NucleusAnimalsCalciumCalcium SignalingCattleCell NucleusCells, CulturedCell SurvivalChelating AgentsEgtazic AcidNFATC Transcription FactorsOligopeptidesOsteoclastsOsteopontinRabbitsRats1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acidarginyl-glycyl-aspartic acidCalciumChelating AgentsEgtazic AcidNFATC Transcription FactorsOligopeptidesOsteopontinSpp1 protein, rat

Identifiers

PMID21940634
PMCPMC3220590
OpenAlexW2006651539

What Socratic 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 Socratic graph.