Evidence map›Paper›PMID 23362087›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2013

Pyk2 regulates megakaryocyte-induced increases in osteoblast number and bone formation.

Ying-Hua Cheng, R Adam Hooker, Khanh Nguyen, Rita Gerard-O'Riley, David L Waning, Brahmananda R Chitteti, Tomas E Meijome, Hui Lin Chua, Artur P Plett, Christie M Orschell and 5 more

Open access · greenAbstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2013. 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
0.9field-weighted citation impact, top 25% 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, 28 citations in OpenAlex.

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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

15 authors at 3 institutions in 2 countries.

Ying-Hua ChengDepartment of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
R Adam Hooker
Khanh Nguyen
Rita Gerard-O'Riley
David L Waning
Brahmananda R Chitteti
Tomas E Meijome
Hui Lin Chua
Artur P Plett
Christie M Orschell
Edward F Srour
Lindsey D Mayo
Fredrick M Pavalko
Angela Bruzzaniti
Melissa A Kacena
Indiana University School of MedicineIndiana University – Purdue University Indianapolis · USJuliana Kinderziekenhuis · NL

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Extrinsic Modulation of Hematopoietic Stem Cell FateR01HL055716 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SROUR, EDWARD F · 1995 to 2010
$2.7M
Multifaceted Interventions to Amplify HSC EngraftmentR01HL075660 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI ORSCHELL, CHRISTIE M · 2005 to 2009
$1.8M
Mechanical Signaling through Osteoblast Focal AdhesionsR01AR052682 · NIAMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI PAVALKO, FREDRICK M · 2007 to 2011
$1.8M
Regulation of Osteoblast Function by Megakaryocytes: Key Signaling ProteinsR01AR060332 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI BRUZZANITI, ANGELA, KACENA, MELISSA A · 2011 to 2015
$1.7M
Regulation of Mdm2 compartmentalizationR01CA109262 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MAYO, LINDSEY D · 2005 to 2009
$1.2M
(PQ9) Novel therapeutic approaches to chemotherapy-induced muscle.R21CA205437 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI WANING, DAVID L · 2016 to 2017
$372k
The Role of OPG in GATA-1 DeficiencyR03AR055269 · NIAMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI KACENA, MELISSA A · 2007 to 2009
$224k
NCI NIH HHS P30 CA082709NCI NIH HHS R01 CA109262NHLBI NIH HHS R01 HL055716NHLBI NIH HHS R01 HL075660NHLBI NIH HHS R01 HL55716NIAMS NIH HHS R01 AR052682NIAMS NIH HHS R01 AR060332NIAMS NIH HHS R03 AR055269
6 · The paper itself

Abstract

Preclinical and clinical evidence from megakaryocyte (MK)-related diseases suggests that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We, therefore, examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 levels in OBs were significantly enhanced primarily because of increased Pyk2 gene transcription. Additionally, p53 and Mdm2 were both decreased in OBs upon MK stimulation, which would be permissive of cell cycle entry. We then demonstrated that OB number was markedly reduced when Pyk2-/- OBs, as opposed to wild-type (WT) OBs, were co-cultured with MKs. We also determined that MKs inhibit OB differentiation in the presence and absence of Pyk2 expression. Finally, given that MK-replete spleen cells from GATA-1-deficient mice can robustly stimulate OB proliferation and bone formation in WT mice, we adoptively transferred spleen cells from these mice into Pyk2-/- recipient mice. Importantly, GATA-1-deficient spleen cells failed to stimulate an increase in bone formation in Pyk2-/- mice, suggesting in vivo the important role of Pyk2 in the MK-induced increase in bone volume. Further understanding of the signaling pathways involved in the MK-mediated enhancement of OB number and bone formation will facilitate the development of novel anabolic therapies to treat bone loss diseases.

Indexed as

AnimalsCell DifferentiationCells, CulturedCoculture TechniquesFocal Adhesion Kinase 2MegakaryocytesMiceMice, KnockoutOsteoblastsOsteogenesisProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53Focal Adhesion Kinase 2Mdm2 protein, mouseProto-Oncogene Proteins c-mdm2Ptk2b protein, mouseTumor Suppressor Protein p53

Identifiers

PMID23362087
PMCPMC3663900
OpenAlexW1905985436

What Socratic 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 Socratic graph.