Evidence map›Paper›PMID 32168373›Full record

ArticleEndocrinology2020

Estrogen Stimulation of Pleiotrophin Enhances Osteoblast Differentiation and Maintains Bone Mass in IGFBP-2 Null Mice.

Gang Xi, Victoria E Demambro, Susan D'Costa, Shalier K Xia, Zach C Cox, Clifford J Rosen, David R Clemmons

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2020. 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
0.9field-weighted citation impact, top 27% 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, 19 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

7 authors at 2 institutions in 1 country.

Gang XiDepartment of Medicine UNC School of Medicine Chapel Hill, North Carolina.
Victoria E DemambroMaine Medical Center Research Institute, Scarborough, Maine.
Susan D'CostaDepartment of Medicine UNC School of Medicine Chapel Hill, North Carolina.
Shalier K XiaDepartment of Medicine UNC School of Medicine Chapel Hill, North Carolina.
Zach C CoxDepartment of Medicine UNC School of Medicine Chapel Hill, North Carolina.
Clifford J RosenMaine Medical Center Research Institute, Scarborough, Maine.
David R ClemmonsDepartment of Medicine UNC School of Medicine Chapel Hill, North Carolina.
University of North Carolina Health Care · USMaine Medical Center Research Institute · US

Funding

Determination of the Mechanisms by which IGFBP-2 Stimulates Bone RemodelingR01AR061164 · NIAMS · MAINEHEALTH · PI CLEMMONS, DAVID ROBERT, ROSEN, CLIFFORD JAMES · 2011 to 2015
$2.4M
NIAMS NIH HHS R01 AR061164
6 · The paper itself

Abstract

Insulin-like growth factor binding protein-2 (IGFBP-2) stimulates osteoblast differentiation but only male Igfbp2 null mice have a skeletal phenotype. The trophic actions of IGFBP-2 in bone are mediated through its binding to receptor tyrosine phosphatase beta (RPTPβ). Another important ligand for RPTPβ is pleiotrophin (PTN), which also stimulates osteoblast differentiation. We determined the change in PTN and RPTPβ in Igfbp2-/- mice. Analysis of whole bone mRNA in wild-type and knockout mice revealed increased expression of Ptn. Rptpβ increased in gene-deleted animals with females having greater expression than males. Knockdown of PTN expression in osteoblasts in vitro inhibited differentiation, and addition of PTN to the incubation medium rescued the response. Estradiol stimulated PTN secretion and PTN knockdown blocked estradiol-stimulated differentiation. PTN addition to IGFBP-2 silenced osteoblast stimulated differentiation, and an anti-fibronectin-3 antibody, which inhibits PTN binding to RPTPβ, inhibited this response. Estrogen stimulated PTN secretion and downstream signaling in the IGFBP-2 silenced osteoblasts and these effects were inhibited with anti-fibronectin-3. Administration of estrogen to wild-type and Igfbp2-/- male mice stimulated an increase in both areal bone mineral density and trabecular bone volume fraction but the increase was significantly greater in the Igfbp2-/- animals. Estrogen also stimulated RPTPβ expression in the null mice. We conclude that loss of IGFBP-2 expression is accompanied by upregulation of PTN and RPTPβ expression in osteoblasts, that the degree of increase is greater in females due to estrogen secretion, and that this compensatory change may account for some component of the maintenance of normal bone mass in female mice.

Indexed as

AnimalsBone DensityCancellous BoneCarrier ProteinsCell DifferentiationCytokinesEstradiolFemaleInsulin-Like Growth Factor Binding Protein 2MaleMiceMice, KnockoutOsteoblastsOsteogenesisPhosphorylationSex FactorsCarrier ProteinsCytokinesEstradiolInsulin-Like Growth Factor Binding Protein 2pleiotrophinbone mineral densityinsulin-like growth factor-1osteocalcinreceptor tyrosine phosphatase betasexual dimophism

Identifiers

PMID32168373
PMCPMC7069688
OpenAlexW3011039736

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.