Evidence map›Paper›PMID 27666759›Full record

ArticleKidney international2017

Ligand trap of the activin receptor type IIA inhibits osteoclast stimulation of bone remodeling in diabetic mice with chronic kidney disease.

Toshifumi Sugatani, Olga A Agapova, Yifu Fang, Alycia G Berman, Joseph M Wallace, Hartmut H Malluche, Marie-Claude Faugere, William Smith, Victoria Sung, Keith A Hruska

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

Article in Kidney international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

34 citing papers in PubMed, 53 citations in OpenAlex.

  1. Serum activin A and bone metabolism in patients undergoing hemodialysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  2. Review
  3. Article
  4. Review
  5. In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.American journal of physiology. Renal physiology · 2024
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  11. Article
  12. Review
  13. Review
  14. Chronic Kidney Disease-Induced Vascular Calcification Impairs Bone Metabolism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Article
  15. Review
  16. Article
  17. Review
  18. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Toshifumi SugataniDepartment of Pediatrics and Medicine, Renal Division, Washington University, St. Louis, Missouri, USA.
Olga A AgapovaDepartment of Pediatrics and Medicine, Renal Division, Washington University, St. Louis, Missouri, USA.
Yifu FangDepartment of Pediatrics and Medicine, Renal Division, Washington University, St. Louis, Missouri, USA.
Alycia G BermanDepartment of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA.
Joseph M WallaceDepartment of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA.
Hartmut H MallucheDivision of Nephrology, Bone and Mineral Metabolism, Department of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Marie-Claude FaugereDivision of Nephrology, Bone and Mineral Metabolism, Department of Medicine, University of Kentucky, Lexington, Kentucky, USA.
William SmithEarly Clinical Development, Celgene Corp., Basking Ridge, New Jersey, USA.
Victoria SungTranslational Medicine, Celgene Corp., San Francisco, California, USA.
Keith A HruskaDepartment of Pediatrics and Medicine, Renal Division, Washington University, St. Louis, Missouri, USA. Electronic address: Hruska_k@kids.wustl.edu.
Indiana University – Purdue University Indianapolis · USUniversity of Indianapolis · USUniversity of Kentucky · USWashington University in St. Louis · US

Funding

The Role of the Osteoblast Secretome in Bone FormationP30AR057235 · NIAMS · WASHINGTON UNIVERSITY · PI SILVA, MATTHEW J · 2009 to 2018
$5.7M
Renal Osteodystrophy: A Fresh ApproachR01DK080770 · NIDDK · UNIVERSITY OF KENTUCKY · PI MALLUCHE, HARTMUT H · 2009 to 2019
$4.8M
RENAL OSTEODYSTROPHY AND VASCULAR CALCIFICATIONR01DK070790 · NIDDK · WASHINGTON UNIVERSITY · PI HRUSKA, KEITH A · 2006 to 2018
$3.9M
CARDIOVASCULAR RISK MECHANISMS IN CKDR01DK089137 · NIDDK · WASHINGTON UNIVERSITY · PI HRUSKA, KEITH A · 2012 to 2016
$1.6M
NIAMS NIH HHS P30 AR057235NIDDK NIH HHS R01 DK070790NIDDK NIH HHS R01 DK080770NIDDK NIH HHS R01 DK089137
6 · The paper itself

Abstract

Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr-/- high fat-fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 mice were given vehicle twice weekly from week 22 until the mice were killed at 28 weeks of age. The animals were then evaluated by skeletal histomorphometry, micro-computed tomography, mechanical strength testing, and ex vivo bone cell culture. Results in the CKD groups were compared with those of the 16 sham-operated ldlr-/- high fat-fed mice. Sham-operated mice had low-turnover osteodystrophy and skeletal frailty. CKD stimulated bone remodeling with significant increases in osteoclast and osteoblast numbers and bone resorption. Compared with mice with CKD and sham-operated mice, RAP-011 treatment eliminated the CKD-induced increase in these histomorphometric parameters and increased trabecular bone fraction. RAP-011 significantly increased cortical bone area and thickness. Activin A-enhanced osteoclastogenesis was mediated through p-Smad2 association with c-fos and activation of nuclear factor of activated T cells c1 (NFATc1). Thus, an ActRIIA ligand trap reversed CKD-stimulated bone remodeling, likely through inhibition of activin-A induced osteoclastogenesis.

Indexed as

ActivinsAnimalsBone RemodelingCells, CulturedChronic Kidney Disease-Mineral and Bone DisorderDiabetes Mellitus, ExperimentalDisease Models, AnimalGlomerular Filtration RateHyperphosphatemiaMaleMiceMice, KnockoutOsteoblastsOsteoclastsReceptors, LDLRecombinant Fusion Proteinsactivin AActivinsActRIIA-mIgG2aFc fusion proteinReceptors, LDLRecombinant Fusion Proteinsactivin Aactivin receptor type IIAchronic kidney diseaserenal osteodystrophysignaling

Identifiers

PMID27666759
PMCPMC5530394
OpenAlexW2522739841

What OpenQuestion holds

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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.