Evidence map›Paper›PMID 23864176›Full record

ArticleThe Journal of bone and joint surgery. American volume2013

Wnt3a reestablishes osteogenic capacity to bone grafts from aged animals.

Philipp Leucht, Jie Jiang, Du Cheng, Bo Liu, Girija Dhamdhere, Mark Yang Fang, Stefanie D Monica, Jonathan J Urena, Whitney Cole, Lane R Smith and 3 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of bone and joint surgery. American volume, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.8field-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

33 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Cellular senescence in skeletal disease: mechanisms and treatment.Cellular & molecular biology letters · 2023
    Review
  3. Article
  4. Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.Journal of tissue engineering and regenerative medicine · 2022
    Review
  5. Hormone sensitive lipase ablation promotes bone regeneration.Biochimica et biophysica acta. Molecular basis of disease · 2022
    Article
  6. Article
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  8. Article
  9. Article
  10. Article
  11. Expanding the phenome and variome of skeletal dysplasia.Genetics in medicine : official journal of the American College of Medical Genetics · 2018
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018
    Article
  17. Article
  18. Article
  19. Biophysical regulation of osteotomy healing: An animal study.Clinical implant dentistry and related research · 2017
    Article
  20. 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

13 authors at 6 institutions in 1 country.

Philipp LeuchtDepartment of Orthopaedic Surgery, Stanford School of Medicine, Stanford, CA 94305, USA.
Jie Jiang
Du Cheng
Bo Liu
Girija Dhamdhere
Mark Yang Fang
Stefanie D Monica
Jonathan J Urena
Whitney Cole
Lane R Smith
Alesha B Castillo
Michael T Longaker
Jill A Helms
Stanford University · USStanford Medicine · USVA Palo Alto Health Care System · USColumbia University · USUniversity of California, Berkeley · USUniversity of California, Los Angeles · US

Funding

Wnt signaling in skeletal tissue regenerationF32AR057648 · NIAMS · STANFORD UNIVERSITY · PI JIANG, JIE · 2009 to 2010
$104k
NIAMS NIH HHS 5F32 AR57648-02
6 · The paper itself

Abstract

backgroundAge-related fatty degeneration of the bone marrow contributes to delayed fracture-healing and osteoporosis-related fractures in the elderly. The mechanisms underlying this fatty change are unknown, but they may relate to the level of Wnt signaling within the aged marrow cavity.

methodsTransgenic mice were used in conjunction with a syngeneic bone-graft model to follow the fates of cells involved in the engraftment. Immunohistochemistry along with quantitative assays were used to evaluate Wnt signaling and adipogenic and osteogenic gene expression in bone grafts from young and aged mice. Liposomal Wnt3a protein (L-Wnt3a) was tested for its ability to restore osteogenic potential to aged bone grafts in critical-size defect models created in mice and in rabbits. Radiography, microquantitative computed tomography (micro-CT) reconstruction, histology, and histomorphometric measurements were used to quantify bone-healing resulting from L-Wnt3a or a control substance (liposomal phosphate-buffered saline solution [L-PBS]).

resultsExpression profiling of cells in a bone graft demonstrated a shift away from an osteogenic gene profile and toward an adipogenic one with age. This age-related adipogenic shift was accompanied by a significant reduction (p < 0.05) in Wnt signaling and a loss in osteogenic potential. In both large and small animal models, osteogenic competence was restored to aged bone grafts by a brief incubation with the stem-cell factor Wnt3a. In addition, liposomal Wnt3a significantly reduced cell death in the bone graft, resulting in significantly more osseous regenerate in comparison with controls.

conclusionsLiposomal Wnt3a enhances cell survival and reestablishes the osteogenic capacity of bone grafts from aged animals. CLINICAL RELEVANCE: We developed an effective, clinically applicable, regenerative medicine-based strategy for revitalizing bone grafts from aged patients.

Indexed as

AdipogenesisAnimalsBone RegenerationBone TransplantationGene ExpressionMiceMice, TransgenicOsteogenesisRabbitsSignal TransductionWnt3A ProteinWnt3A Protein

Identifiers

PMID23864176
PMCPMC3748990
OpenAlexW2144960267

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.