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Genetic deficiency of Wnt5a diminishes disease severity in a murine model of rheumatoid arthritis

Overview of attention for article published in Arthritis Research & Therapy, July 2017
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Title
Genetic deficiency of Wnt5a diminishes disease severity in a murine model of rheumatoid arthritis
Published in
Arthritis Research & Therapy, July 2017
DOI 10.1186/s13075-017-1375-0
Pubmed ID
Authors

Susan MacLauchlan, Maria A. Zuriaga, José J. Fuster, Carla M. Cuda, Jennifer Jonason, Fernanda Behzadi, Jennifer Parker Duffen, G. Kenneth Haines, Tamar Aprahamian, Harris Perlman, Kenneth Walsh

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Despite the recent successes of disease-modifying anti-rheumatic drugs (DMARDs), there is still clinical need for understanding the development and molecular etiology of RA. Wnts are developmental morphogens whose roles in adult pathology are poorly characterized. Wnt5a is a member of the non-canonical family of Wnts that modulates a wide range of cell processes, including differentiation, migration, and inflammation. Wnt5a has been implicated as a possible contributor to arthritis and it is upregulated in synovial fibroblasts from RA patients. We investigated the role of endogenous Wnt5a in RA. Tamoxifen-inducible, Wnt5a knockout (Wnt5a cKO) mice and littermate controls were monitored for arthritis development and joint pathology using the K/BxN serum transfer-induced arthritis (STIA) model. To explore a role of Wnt5a in osteoclast fusion, bone marrow-derived monocytes (BMDMs) were differentiated in vitro. Wnt5a cKO mice were resistant to arthritis development compared to control littermates as assessed by ankle thickness and histologic measurements. Some parameters of inflammation were reduced in the Wnt5a cKO mice, including the extent of polymononuclear cell infiltration and extra-articular inflammation. Wnt5a cKO mice also exhibited less cartilage destruction and a reduction in osteoclast activity with concomitant reduction in tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), macrophage colony-stimulating factor (MCSF), matrix metalloproteinase (MMP)2 and MMP9 in the arthritic joints. Treatment of BMDMs with Wnt5a enhanced osteoclast fusion and increased the expression of dendrocyte-expressed seven transmembrane protein (DCSTAMP) and MMP9, that are necessary for osteoclast formation and activity. These data suggest that Wnt5a modulates the development of arthritis by promoting inflammation and osteoclast fusion, and provide the first mouse genetic evidence of a role for endogenous Wnt5a in autoimmune disease.

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The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 54 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 20%
Researcher 4 7%
Student > Doctoral Student 4 7%
Student > Bachelor 4 7%
Student > Postgraduate 3 6%
Other 10 19%
Unknown 18 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 24%
Medicine and Dentistry 11 20%
Agricultural and Biological Sciences 4 7%
Nursing and Health Professions 2 4%
Unspecified 2 4%
Other 5 9%
Unknown 17 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 June 2019.
All research outputs
#8,476,767
of 25,382,440 outputs
Outputs from Arthritis Research & Therapy
#1,696
of 3,380 outputs
Outputs of similar age
#125,091
of 325,062 outputs
Outputs of similar age from Arthritis Research & Therapy
#31
of 58 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 3,380 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 325,062 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.