Evidence map›Paper›PMID 25656774›Full record

ArticleJournal of cellular physiology2015

A novel role for thrombopoietin in regulating osteoclast development in humans and mice.

Monique Bethel, Calvin L T Barnes, Amanda F Taylor, Ying-Hua Cheng, Brahmananda R Chitteti, Mark C Horowitz, Angela Bruzzaniti, Edward F Srour, Melissa A Kacena

Open access · greenAbstract read
In one paragraph

Article in Journal of cellular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 28% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Thrombopoietic agents enhance bone healing in mice, rats, and pigs.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Article
  4. Review
  5. Review
  6. Article
  7. Neonatal Osteomacs and Bone Marrow Macrophages Differ in Phenotypic Marker Expression and Function.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Article
  8. Making Sense of the Highly Variable Effects of Alcohol on Bone.Clinical reviews in bone and mineral metabolism · 2021
    Article
  9. Article
  10. Article
  11. 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.

Monique BethelDepartment of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Calvin L T BarnesDepartment of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut.
Amanda F TaylorDepartment of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Ying-Hua ChengDepartment of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Brahmananda R ChittetiDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Mark C HorowitzDepartment of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut.
Angela BruzzanitiDepartment of Oral Biology, Indiana University School of Dentistry, Indianapolis, Indiana.
Edward F SrourDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Melissa A KacenaDepartment of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineYale University · US

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Project-005U54DK106846 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Reuben Kapur, Karen Elizabeth Pollok · 2015 to 2026
$9.7M
BASIC SCIENCE STUDIES ON GENE THERAPY OF BLOOD DISEASEST32HL007910 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Roland W. Herzog, Reuben Kapur · 1999 to 2026
$7.6M
Regulating hematopoietic stem cells and hematopoiesis for clinical efficacyP30DK090948 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI BROXMEYER, HAL E., SROUR, EDWARD F · 2010 to 2014
$3.7M
Regulation of Osteoblast Function by Megakaryocytes: Key Signaling ProteinsR01AR060332 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI BRUZZANITI, ANGELA, KACENA, MELISSA A · 2011 to 2015
$1.7M
Thrombopoietin: A novel regulator of bone healingR01AR060863 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI KACENA, MELISSA A · 2012 to 2016
$1.7M
NCATS NIH HHS UL1 TR001108NCATS NIH HHS UL1TR001108NCI NIH HHS P30 CA082709NHLBI NIH HHS T32 HL007910NIAMS NIH HHS R01 AR060332NIAMS NIH HHS R01 AR060863NIDDK NIH HHS P30 DK090948NIDDK NIH HHS U54 DK106846
6 · The paper itself

Abstract

Emerging data suggest that megakaryocytes (MKs) play a significant role in skeletal homeostasis. Indeed, osteosclerosis observed in several MK-related disorders may be a result of increased numbers of MKs. In support of this idea, we have previously demonstrated that MKs increase osteoblast (OB) proliferation by a direct cell-cell contact mechanism and that MKs also inhibit osteoclast (OC) formation. As MKs and OCs are derived from the same hematopoietic precursor, in these osteoclastogenesis studies we examined the role of the main MK growth factor, thrombopoietin (TPO) on OC formation and bone resorption. Here we show that TPO directly increases OC formation and differentiation in vitro. Specifically, we demonstrate the TPO receptor (c-mpl or CD110) is expressed on cells of the OC lineage, c-mpl is required for TPO to enhance OC formation in vitro, and TPO activates the mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and nuclear factor-kappaB signaling pathways, but does not activate the PI3K/AKT pathway. Further, we found TPO enhances OC resorption in CD14+CD110+ human OC progenitors derived from peripheral blood mononuclear cells, and further separating OC progenitors based on CD110 expression enriches for mature OC development. The regulation of OCs by TPO highlights a novel therapeutic target for bone loss diseases and may be important to consider in the numerous hematologic disorders associated with alterations in TPO/c-mpl signaling as well as in patients suffering from bone disorders.

Indexed as

AnimalsCell DifferentiationCell LineageCell ProliferationHematopoiesisHumansMegakaryocytesMiceMice, KnockoutOsteoclastsReceptors, ThrombopoietinRecombinant ProteinsSignal TransductionStem CellsThrombopoietinMpl protein, mouseReceptors, ThrombopoietinRecombinant ProteinsThrombopoietin

Identifiers

PMID25656774
PMCPMC4447549
OpenAlexW2123095869

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.