Evidence map›Paper›PMID 36631218›Full record

ArticleLife science alliance2023

Functional substitutions of amino acids that differ between GDF11 and GDF8 impact skeletal development and skeletal muscle.

John Lian, Ryan G Walker, Andrea D'Amico, Ana Vujic, Melanie J Mills, Kathleen A Messemer, Kourtney R Mendello, Jill M Goldstein, Krystynne A Leacock, Soraya Epp and 4 more

Abstract read
In one paragraph

Article in Life science alliance, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. [Growth differentiation factor 11 attenuates hypoxia/reoxygenation injury in rat H9C2 cardiomyocytesNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
    Article
  2. Article
  3. GDF11-secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  4. GDF10 promotes rodent cardiomyocyte maturation during the postnatal period.Journal of molecular and cellular cardiology · 2025
    Article
  5. GDF11 and aging biology - controversies resolved and pending.The journal of cardiovascular aging · 2023
    Article
  6. GDF-11 as a Potential Cardiac Pro-Angiogenic Factor.JACC. Basic to translational science · 2023
    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

14 authors.

John LianDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.ORCID https://orcid.org/0000-0002-6512-646X
Ryan G WalkerDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.ORCID https://orcid.org/0000-0001-6160-8026
Andrea D'AmicoDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.ORCID https://orcid.org/0000-0002-8188-4674
Ana VujicDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.ORCID https://orcid.org/0000-0002-0559-5299
Melanie J MillsDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Kathleen A MessemerDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Kourtney R MendelloDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Jill M GoldsteinDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Krystynne A LeacockDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.ORCID https://orcid.org/0000-0002-5909-4596
Soraya EppDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Emma V StimpflDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Thomas B ThompsonDepartment of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH, USA.
Amy J WagersDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.ORCID https://orcid.org/0000-0002-0066-0485
Richard T LeeDepartment of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA richard_lee@harvard.edu amy_wagers@harvard.edu.ORCID https://orcid.org/0000-0003-4687-1381

Funding

MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
Regulation and Function of Growth Differentiation Factor 11 During Development and AgingR01AG048917 · NIA · HARVARD UNIVERSITY · PI WAGERS, AMY JO · 2016 to 2020
$2.8M
Regulation of GDF11 by extracellular mechanismsR01AG072087 · NIA · UNIVERSITY OF CINCINNATI · PI THOMPSON, THOMAS B · 2020 to 2024
$2.8M
Structural/functional characterization of TGFβ superfamily signaling and regulationR35GM134923 · NIGMS · UNIVERSITY OF CINCINNATI · PI THOMPSON, THOMAS B · 2020 to 2024
$2.6M
Investigating GDF11 and MSTN as candidate circulating geronic factorsR01AG057428 · NIA · HARVARD UNIVERSITY · PI WAGERS, AMY JO · 2017 to 2020
$2.0M
A New Pathway for Reversing Cardiac AgingR01AG047131 · NIA · HARVARD UNIVERSITY · PI LEE, RICHARD T · 2015 to 2019
$1.7M
In vivo Structure-Function relationships of GDF11 and GDF8R56AG062468 · NIA · HARVARD UNIVERSITY · PI LEE, RICHARD T · 2020 to 2020
$346k
NHLBI NIH HHS T32 HL007208NIA NIH HHS R01 AG047131NIA NIH HHS R01 AG048917NIA NIH HHS R01 AG057428NIA NIH HHS R01 AG072087NIA NIH HHS R56 AG062468NIGMS NIH HHS R35 GM134923
6 · The paper itself

Abstract

Growth differentiation factor 11 (GDF11) and GDF8 (MSTN) are closely related TGF-β family proteins that interact with nearly identical signaling receptors and antagonists. However, GDF11 appears to activate SMAD2/3 more potently than GDF8 in vitro and in vivo. The ligands possess divergent structural properties, whereby substituting unique GDF11 amino acids into GDF8 enhanced the activity of the resulting chimeric GDF8. We investigated potentially distinct endogenous activities of GDF11 and GDF8 in vivo by genetically modifying their mature signaling domains. Full recoding of GDF8 to that of GDF11 yielded mice lacking GDF8, with GDF11 levels ∼50-fold higher than normal, and exhibiting modestly decreased muscle mass, with no apparent negative impacts on health or survival. Substitution of two specific amino acids in the fingertip region of GDF11 with the corresponding GDF8 residues resulted in prenatal axial skeletal transformations, consistent with

Indexed as

Bone DevelopmentGrowth Differentiation FactorsMuscle, SkeletalMyostatinAmino AcidsAnimalsBone Morphogenetic ProteinsFemaleMicePregnancyTransforming Growth Factor betaAmino AcidsBone Morphogenetic ProteinsGdf11 protein, mouseGrowth Differentiation FactorsMstn protein, mouseMyostatinTransforming Growth Factor beta

Identifiers

PMID36631218
PMCPMC9834663

What OpenQuestion holds

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Registered trials

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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.