Evidence map›Paper›PMID 24994594›Full record

ArticleBone2014

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.

Naga Suresh Adapala, Danielle Holland, Vanessa Scanlon, Mary F Barbe, Wallace Y Langdon, Alexander Y Tsygankov, Joseph A Lorenzo, Archana Sanjay

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bone, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Research progress on the regulation of miRNAs in diabetic kidney disease and osteoporosis.International journal of clinical and experimental pathology · 2026
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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 3 institutions in 2 countries.

Naga Suresh AdapalaDepartment of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06032, USA.
Danielle HollandDepartment of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Vanessa ScanlonDepartment of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06032, USA.
Mary F BarbeDepartment of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Wallace Y LangdonSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley 6009, Australia.
Alexander Y TsygankovDepartment of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Joseph A LorenzoDepartment of Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA.
Archana SanjayDepartment of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06032, USA. Electronic address: asanjay@uchc.edu.
UConn Health · USTemple University · USThe University of Western Australia · AU

Funding

Skeletal, Craniofacial and Oral Biology Training GrantT90DE021989 · NIDCR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI MINA, MINA · 2011 to 2022
$4.5M
Regulation of Osteoclast Function : Role of the Cbl-PI3K ComplexR01AR055601 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI SANJAY, ARCHANA · 2008 to 2012
$1.6M
NIAMS NIH HHS AR0550601NIAMS NIH HHS R01 AR055601NIDCR NIH HHS T90 DE021989
6 · The paper itself

Abstract

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl-/- mice have delayed bone development due to decreased osteoclast migration. Cbl-b-/- mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl-/- and Cbl-b-/- mice showed significant bone loss in the tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy.

Indexed as

AnimalsBone ResorptionCollagen Type IFemaleMiceMice, KnockoutOvariectomyPeptidesPhosphatidylinositol 3-KinasesProtein BindingProto-Oncogene Proteins c-cblCollagen Type Icollagen type I trimeric cross-linked peptidePeptidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-cblBone resorptionCblCbl-bOsteoclastOvariectomyPI3K

Identifiers

PMID24994594
PMCPMC4149851
OpenAlexW1973753118

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.