Evidence map›Paper›PMID 27937051›Full record

ArticleConnective tissue research2017

Wnt10b and Dkk-1 gene therapy differentially influenced trabecular bone architecture, soft tissue integrity, and osteophytosis in a skeletally mature rat model of osteoarthritis.

Jeffrey B Mason, Brittney L Gurda, Kurt D Hankenson, Lindsey R Harper, Cathy S Carlson, James M Wilson, Dean W Richardson

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

Article in Connective tissue research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 18% 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

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. WNT Signalling in Osteoarthritis and Its Pharmacological Targeting.Handbook of experimental pharmacology · 2021
    Review
  4. Review
  5. 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

7 authors at 2 institutions in 1 country.

Jeffrey B Masona Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine , University of Pennsylvania , Philadelphia , PA , USA.
Brittney L Gurdac Gene Therapy Program, School of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
Kurt D Hankensona Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine , University of Pennsylvania , Philadelphia , PA , USA.
Lindsey R Harperd Department of Veterinary Population Medicine, College of Veterinary Medicine , University of Minnesota , St. Paul , MN , USA.
Cathy S Carlsond Department of Veterinary Population Medicine, College of Veterinary Medicine , University of Minnesota , St. Paul , MN , USA.
James M Wilsonc Gene Therapy Program, School of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
Dean W Richardsona Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine , University of Pennsylvania , Philadelphia , PA , USA.
University of Pennsylvania · USUniversity of Minnesota · US

Funding

Vector CoreP30DK047757 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LIMBERIS, MARIA P. · 1993 to 2017
$18.0M
In Vivo Gene Therapy for Treatment of OsteoarthritisF32AR056936 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MASON, JEFFREY B. · 2010 to 2012
$163k
NIAMS NIH HHS F32 AR056936NIDDK NIH HHS P30 DK047757
6 · The paper itself

Abstract

aimsOur goals in the current experiments were to determine if (a) upregulation of Wnt signaling would induce osteoarthritis changes in stable stifle joints and (b) if downregulation of Wnt signaling in destabilized joints would influence the progression of OA.

methodsAt 37 weeks of age, rats were injected in the stifle joint with a recombinant adeno-associated viral vector containing the Wnt-inhibitor Dkk-1 or a Wnt10b transgene. At 40 weeks of age, rats underwent surgical destabilization of the joint. At 50 weeks of age, stifle joints were submitted for micro-computed tomography and histopathological analysis.

resultsInjection of either Wnt10b or Dkk-1 transgenes in stable joints improved bone architectural parameters, but worsened soft tissue integrity. Osteophytosis was decreased by Dkk-1, but unchanged by Wnt10b. Destabilization negatively influenced bone architecture, increased osteophytosis, and decreased soft tissue integrity. Dkk-1 exacerbated the negative effects of destabilization, whereas Wnt10b had little effect on these parameters. Osteophytosis was improved, whereas soft tissue integrity was worsened by both transgenes in destabilized joints.

conclusionsThe Wnt-inhibitor Dkk-1 does not appear to completely inhibit the effects of Wnt signaling on bone remodeling. In vivo upregulation of Wnt10b and its inhibitor, Dkk-1, can produce both parallel or contrasting phenotypic responses depending on the specific parameter measured and the fidelity of the examined joint. These observations elucidate different roles for Wnt signaling in stable versus destabilized joints and may help to explain the conflicting results previously reported for the role of Dkk-1 in joint disease.

Indexed as

Genetic TherapyAnimalsBone RemodelingCancellous BoneCartilage, ArticularChondrocytesDisease Models, AnimalIntercellular Signaling Peptides and ProteinsKnee JointMaleOsteoarthritis, KneeProto-Oncogene ProteinsRats, Sprague-DawleyWnt ProteinsDkk1 protein, ratIntercellular Signaling Peptides and ProteinsProto-Oncogene ProteinsWNT10B protein, humanWnt ProteinsCartilagegene therapyosteoarthritisosteophyteWnt/Dkk-1 pathway

Identifiers

PMID27937051
PMCPMC7413086
OpenAlexW2565898677

What OpenQuestion holds

Textmetadata
LicenceTDM
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.