Evidence map›Paper›PMID 26264579›Full record

ArticleHuman molecular genetics2015

Altered cytoskeletal organization characterized lethal but not surviving Brtl+/- mice: insight on phenotypic variability in osteogenesis imperfecta.

Laura Bianchi, Assunta Gagliardi, Silvia Maruelli, Roberta Besio, Claudia Landi, Roberta Gioia, Kenneth M Kozloff, Basma M Khoury, Paul J Coucke, Sofie Symoens and 4 more

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

Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Cells · 2025
    Article
  5. Article
  6. Article
  7. Observational
  8. Article
  9. Review
  10. CaMKII inhibition due to TRIC-B loss-of-function dysregulates SMAD signaling in osteogenesis imperfecta.Matrix biology : journal of the International Society for Matrix Biology · 2023
    Article
  11. Article
  12. Review
  13. Article
  14. Antagonism Between PEDF and TGF-β Contributes to Type VI Osteogenesis Imperfecta Bone and Vascular Pathogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  15. Review
  16. Article
  17. Review
  18. Article
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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

14 authors at 6 institutions in 3 countries.

Laura BianchiFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Siena, Italy.
Assunta GagliardiFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Siena, Italy.
Silvia MaruelliDepartment of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.
Roberta BesioDepartment of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.
Claudia LandiFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Siena, Italy.
Roberta GioiaDepartment of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.
Kenneth M KozloffOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Basma M KhouryOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Paul J CouckeCenter for Medical Genetics, Ghent University, Ghent, Belgium and.
Sofie SymoensCenter for Medical Genetics, Ghent University, Ghent, Belgium and.
Joan C MariniBone and Extracellular Matrix Branch, NICHD, National Institute of Health, Bethesda, MD, USA.
Antonio RossiDepartment of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.
Luca BiniFunctional Proteomics Laboratory, Department of Life Sciences, University of Siena, Siena, Italy.
Antonella ForlinoDepartment of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy, aforlino@unipv.it.
University of Pavia · ITUniversity of Siena · ITGhent University Hospital · BEEunice Kennedy Shriver National Institute of Child Health and Human Development · USOrthopaedic Research Laboratories · USUniversity of Michigan–Ann Arbor · US

Funding

Telethon GGP13098
6 · The paper itself

Abstract

Osteogenesis imperfecta (OI) is a heritable bone disease with dominant and recessive transmission. It is characterized by a wide spectrum of clinical outcomes ranging from very mild to lethal in the perinatal period. The intra- and inter-familiar OI phenotypic variability in the presence of an identical molecular defect is still puzzling to the research field. We used the OI murine model Brtl(+/-) to investigate the molecular basis of OI phenotypic variability. Brtl(+/-) resembles classical dominant OI and shows either a moderately severe or a lethal outcome associated with the same Gly349Cys substitution in the α1 chain of type I collagen. A systems biology approach was used. We took advantage of proteomic pathway analysis to functionally link proteins differentially expressed in bone and skin of Brtl(+/-) mice with different outcomes to define possible phenotype modulators. The skin/bone and bone/skin hybrid networks highlighted three focal proteins: vimentin, stathmin and cofilin-1, belonging to or involved in cytoskeletal organization. Abnormal cytoskeleton was indeed demonstrated by immunohistochemistry to occur only in tissues from Brtl(+/-) lethal mice. The aberrant cytoskeleton affected osteoblast proliferation, collagen deposition, integrin and TGF-β signaling with impairment of bone structural properties. Finally, aberrant cytoskeletal assembly was detected in fibroblasts obtained from lethal, but not from non-lethal, OI patients carrying an identical glycine substitution. Our data demonstrated that compromised cytoskeletal assembly impaired both cell signaling and cellular trafficking in mutant lethal mice, altering bone properties. These results point to the cytoskeleton as a phenotypic modulator and potential novel target for OI treatment.

Indexed as

14-3-3 ProteinsAnimalsBone and BonesCofilin 1Collagen Type ICollagen Type I, alpha 1 ChainCytoskeletal ProteinsCytoskeletonDisease Models, AnimalFibroblastsGenes, LethalHumansIntegrinsMiceMice, Mutant StrainsMutation14-3-3 ProteinsCfl1 protein, mouseCofilin 1Collagen Type ICollagen Type I, alpha 1 ChainCytoskeletal ProteinsIntegrinsSfn protein, mouseVimentin

Identifiers

PMID26264579
PMCPMC4607742
OpenAlexW2162026150

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.